Multiple Myeloma

Photo by Jen Smith

SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.

Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.

The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).

Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).

Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.

The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.

Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.

Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.

“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.

Results

The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.

The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.

Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.

Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.

Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.

“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.

He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.

Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).

There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).

In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”

He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.

In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.

Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.

*Data in the abstract differ from the presentation.

Photo by Jen Smith

SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.

Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.

The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).

Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).

Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.

The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.

Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.

Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.

“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.

Results

The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.

The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.

Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.

Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.

Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.

“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.

He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.

Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).

There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).

In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”

He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.

In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.

Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.

*Data in the abstract differ from the presentation.

Photo by Jen Smith

SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.

Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.

The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).

Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).

Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.

The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.

Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.

Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.

“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.

Results

The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.

The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.

Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.

Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.

Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.

“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.

He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.

Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).

There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).

In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”

He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.

In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.

Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.

*Data in the abstract differ from the presentation.

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

Photo by Jen Smith

SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.

Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.

The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.

Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*

Patients

As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).

Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.

All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.

Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.

Treatment

Patients were treated in two concurrent cohorts.

One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.

The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

Safety

Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:

• Nausea (60%)
• Diarrhea (32%)
• Anorexia (28%)
• Vomiting (24%)
• Dysgeusia (20%)
• Fatigue (48%)
• Hyponatremia (28%)
• Insomnia (24%)
• Blurred vision (24%)
• Thrombocytopenia (64%)
• Anemia (48%)
• Leukopenia (44%)
• Neutropenia (44%)
• Lymphopenia (20%).

“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.

The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.

Efficacy

The median follow-up was 7.7 months, and the median time on study was 5.8 months.

Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.

The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.

Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.

Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.

Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).

One patient with a minimal response progressed, and one discontinued treatment due to an AE.

The median progression-free survival was not reached.

“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.

She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.

*Data in the presentation differ from the abstract.

Photo by Jen Smith

SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.

Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.

The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.

Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*

Patients

As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).

Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.

All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.

Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.

Treatment

Patients were treated in two concurrent cohorts.

One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.

The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

Safety

Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:

• Nausea (60%)
• Diarrhea (32%)
• Anorexia (28%)
• Vomiting (24%)
• Dysgeusia (20%)
• Fatigue (48%)
• Hyponatremia (28%)
• Insomnia (24%)
• Blurred vision (24%)
• Thrombocytopenia (64%)
• Anemia (48%)
• Leukopenia (44%)
• Neutropenia (44%)
• Lymphopenia (20%).

“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.

The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.

Efficacy

The median follow-up was 7.7 months, and the median time on study was 5.8 months.

Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.

The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.

Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.

Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.

Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).

One patient with a minimal response progressed, and one discontinued treatment due to an AE.

The median progression-free survival was not reached.

“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.

She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.

*Data in the presentation differ from the abstract.

Photo by Jen Smith

SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.

Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.

The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.

Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*

Patients

As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).

Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.

All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.

Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.

Treatment

Patients were treated in two concurrent cohorts.

One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.

The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.

Safety

Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:

• Nausea (60%)
• Diarrhea (32%)
• Anorexia (28%)
• Vomiting (24%)
• Dysgeusia (20%)
• Fatigue (48%)
• Hyponatremia (28%)
• Insomnia (24%)
• Blurred vision (24%)
• Thrombocytopenia (64%)
• Anemia (48%)
• Leukopenia (44%)
• Neutropenia (44%)
• Lymphopenia (20%).

“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.

The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.

Efficacy

The median follow-up was 7.7 months, and the median time on study was 5.8 months.

Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.

The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.

Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.

Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.

Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).

One patient with a minimal response progressed, and one discontinued treatment due to an AE.

The median progression-free survival was not reached.

“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.

She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.

*Data in the presentation differ from the abstract.

SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.

In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).

With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.

Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.

The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.

The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.

In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.

The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.

[email protected]

SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.

In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).

With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.

Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.

The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.

The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.

In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.

The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.

[email protected]

SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.

In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).

With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.

Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.

The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.

The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.

In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.

The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.

[email protected]

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..






 

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..






 

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..