Multiple Myeloma

Photo by Rhoda Baer

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have called for renewed political commitment to improve cancer services and reduce cancer deaths.

ASCO and ESMO issued a joint statement in which they asked heads of state and health ministers to attend the United Nations Civil Society Hearing on Non-communicable Diseases (NCDs) in September and reconfirm their commitment to “pass legislation and invest in actions that will reduce the burden of NCDs, including cancer.”

Specifically, ESMO and ASCO said governments should:

1. Implement the 2017 World Health Assembly Cancer Resolution
2. Develop and strengthen educational programs that provide lifestyle recommendations to reduce cancer risk (eg, prevent tobacco use, encourage healthy weight control, etc.)
3. Develop efficient and cost-effective primary prevention measures (eg, Helicobacter pylori eradication)
4. Ensure timely access to screening, early stage diagnosis, and treatment for all stages of cancer
5. Strengthen health systems so they can provide cancer services to all who need them
6. Provide essential secondary healthcare services that ensure an adequate number of well-trained oncology professionals who have access to necessary resources
7. Aim to reduce premature mortality by 25% by 2025 and by 33% by 2030 across all NCDs.

“Recent UN and WHO reports^1,2,3,4 note that, unless countries significantly scale-up their actions and investments, they will not meet agreed targets to reduce deaths from non-communicable diseases,” said ESMO President Josep Tabernero, MD, PhD.

“We are concerned that governments may find it easier to achieve their targets by reducing deaths from only some NCDs, leaving cancer patients behind. We believe there are cost-effective ways to improve cancer care and stand ready to assist countries in doing this by providing our expertise in cancer management to support implementation of the 2017 World Health Assembly Cancer Resolution.”

“We urge member states to consider our joint call and amendments to strengthen the political declaration to be approved during the UN high-level meeting on 27 September and thus change the future outlook for cancer patients worldwide.”

1. United Nations Report by the Secretary General, Document A_72_662, 21 December 2017: http://www.who.int/ncds/governance/high-level-commission/A_72_662.pdf

2. World Health Assembly Report by the WHO Director General, Document WHA 71.2, 26 May 2018: http://apps.who.int/gb/ebwha/pdf_files/WHA71/A71_R2-en.pdf

3. WHO Independent High-Level Commission on NCDs Report, Time to Deliver, 1 June 2018: http://apps.who.int/iris/bitstream/handle/10665/272710/9789241514163-eng.pdf?ua=1

4. WHO Report Saving Lives, Spending Less, 21 May 2018: http://apps.who.int/iris/bitstream/handle/10665/272534/WHO-NMH-NVI-18.8-eng.pdf

Photo by Rhoda Baer

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have called for renewed political commitment to improve cancer services and reduce cancer deaths.

ASCO and ESMO issued a joint statement in which they asked heads of state and health ministers to attend the United Nations Civil Society Hearing on Non-communicable Diseases (NCDs) in September and reconfirm their commitment to “pass legislation and invest in actions that will reduce the burden of NCDs, including cancer.”

Specifically, ESMO and ASCO said governments should:

1. Implement the 2017 World Health Assembly Cancer Resolution
2. Develop and strengthen educational programs that provide lifestyle recommendations to reduce cancer risk (eg, prevent tobacco use, encourage healthy weight control, etc.)
3. Develop efficient and cost-effective primary prevention measures (eg, Helicobacter pylori eradication)
4. Ensure timely access to screening, early stage diagnosis, and treatment for all stages of cancer
5. Strengthen health systems so they can provide cancer services to all who need them
6. Provide essential secondary healthcare services that ensure an adequate number of well-trained oncology professionals who have access to necessary resources
7. Aim to reduce premature mortality by 25% by 2025 and by 33% by 2030 across all NCDs.

“Recent UN and WHO reports^1,2,3,4 note that, unless countries significantly scale-up their actions and investments, they will not meet agreed targets to reduce deaths from non-communicable diseases,” said ESMO President Josep Tabernero, MD, PhD.

“We are concerned that governments may find it easier to achieve their targets by reducing deaths from only some NCDs, leaving cancer patients behind. We believe there are cost-effective ways to improve cancer care and stand ready to assist countries in doing this by providing our expertise in cancer management to support implementation of the 2017 World Health Assembly Cancer Resolution.”

“We urge member states to consider our joint call and amendments to strengthen the political declaration to be approved during the UN high-level meeting on 27 September and thus change the future outlook for cancer patients worldwide.”

1. United Nations Report by the Secretary General, Document A_72_662, 21 December 2017: http://www.who.int/ncds/governance/high-level-commission/A_72_662.pdf

2. World Health Assembly Report by the WHO Director General, Document WHA 71.2, 26 May 2018: http://apps.who.int/gb/ebwha/pdf_files/WHA71/A71_R2-en.pdf

3. WHO Independent High-Level Commission on NCDs Report, Time to Deliver, 1 June 2018: http://apps.who.int/iris/bitstream/handle/10665/272710/9789241514163-eng.pdf?ua=1

4. WHO Report Saving Lives, Spending Less, 21 May 2018: http://apps.who.int/iris/bitstream/handle/10665/272534/WHO-NMH-NVI-18.8-eng.pdf

Photo by Rhoda Baer

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have called for renewed political commitment to improve cancer services and reduce cancer deaths.

ASCO and ESMO issued a joint statement in which they asked heads of state and health ministers to attend the United Nations Civil Society Hearing on Non-communicable Diseases (NCDs) in September and reconfirm their commitment to “pass legislation and invest in actions that will reduce the burden of NCDs, including cancer.”

Specifically, ESMO and ASCO said governments should:

1. Implement the 2017 World Health Assembly Cancer Resolution
2. Develop and strengthen educational programs that provide lifestyle recommendations to reduce cancer risk (eg, prevent tobacco use, encourage healthy weight control, etc.)
3. Develop efficient and cost-effective primary prevention measures (eg, Helicobacter pylori eradication)
4. Ensure timely access to screening, early stage diagnosis, and treatment for all stages of cancer
5. Strengthen health systems so they can provide cancer services to all who need them
6. Provide essential secondary healthcare services that ensure an adequate number of well-trained oncology professionals who have access to necessary resources
7. Aim to reduce premature mortality by 25% by 2025 and by 33% by 2030 across all NCDs.

“Recent UN and WHO reports^1,2,3,4 note that, unless countries significantly scale-up their actions and investments, they will not meet agreed targets to reduce deaths from non-communicable diseases,” said ESMO President Josep Tabernero, MD, PhD.

“We are concerned that governments may find it easier to achieve their targets by reducing deaths from only some NCDs, leaving cancer patients behind. We believe there are cost-effective ways to improve cancer care and stand ready to assist countries in doing this by providing our expertise in cancer management to support implementation of the 2017 World Health Assembly Cancer Resolution.”

“We urge member states to consider our joint call and amendments to strengthen the political declaration to be approved during the UN high-level meeting on 27 September and thus change the future outlook for cancer patients worldwide.”

1. United Nations Report by the Secretary General, Document A_72_662, 21 December 2017: http://www.who.int/ncds/governance/high-level-commission/A_72_662.pdf

2. World Health Assembly Report by the WHO Director General, Document WHA 71.2, 26 May 2018: http://apps.who.int/gb/ebwha/pdf_files/WHA71/A71_R2-en.pdf

3. WHO Independent High-Level Commission on NCDs Report, Time to Deliver, 1 June 2018: http://apps.who.int/iris/bitstream/handle/10665/272710/9789241514163-eng.pdf?ua=1

4. WHO Report Saving Lives, Spending Less, 21 May 2018: http://apps.who.int/iris/bitstream/handle/10665/272534/WHO-NMH-NVI-18.8-eng.pdf

Photo from EHA

STOCKHOLM—The alkylating peptide melflufen has demonstrated activity in patients with treatment-resistant multiple myeloma (MM).

In a phase 2 trial, melflufen plus dexamethasone produced an overall response rate (ORR) of 32.1% in MM patients who were refractory to pomalidomide and/or daratumumab and had failed treatment with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs).

Nearly all patients experienced an adverse event (AE) related to study treatment, and most of these were hematologic events.

These results, from the ongoing HORIZON trial, were presented at the 23rd Congress of the European Hematology Association (EHA) as abstract PF581.

The research was sponsored by Oncopeptides AB, the company developing melflufen.

“With an increasing number of patients with highly resistant myeloma, there is a real need for additional treatment options based on new mechanisms of action,” said study investigator Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“[Melflufen], a peptidase-enhanced compound, with its potent activity, manageable tolerability, and lack of shared resistance mechanisms with other modalities, is a promising molecule that is making encouraging progress in clinical development.”

Patients and treatment

The data presented at EHA include 62 patients. The data cut-off was May 10, 2018.

The patients had a median age of 62.5 (range, 41-82), 54% had high-risk cytogenetics, and 46% were ISS stage III. The patients had a median of 5.5 prior lines of therapy, and their median time since initial diagnosis was 6.1 years.

All patients were refractory to pomalidomide or daratumumab, 56% were refractory to both drugs, and 89% were double-refractory to IMiDs and PIs. Ninety-eight percent of patients had disease progression on or within 60 days of completing their last therapy.

Patients received melflufen at 40 mg (intravenously over 30 minutes) on day 1 of each 28-day cycle. They also received dexamethasone at 40 mg weekly. Patients were treated until disease progression, unacceptable toxicity, or withdrawal of consent.

At the data cutoff, 49 patients (79%) had completed at least 2 cycles of melflufen. The median number of cycles was 2 (range, 1-11).

Twenty-one patients (34%) were still receiving study treatment at the data cutoff. Reasons for discontinuation included disease progression (47%), AEs (15%), and physician decision (3%). One discontinuation was due to patient request.

Results

Fifty-six patients received at least 1 dose of melflufen and were evaluable for response.

The ORR was 32.1%, and the clinical benefit rate was 39.3%. ORR was defined as partial response (PR) or better, and clinical benefit rate was defined as minor response or better.

Two percent of patients had a complete response, 9% had a very good PR, 21% had a PR, and 7% had a minor response. Forty-five percent of patients had stable disease, and 16% progressed.

Subgroup analyses showed that response didn’t vary across refractory subsets, but it did vary according to the underlying disease and health status of the patient.

Treatment-related AEs occurred in 97% of all patients (60/62), and grade 3/4 treatment-related AEs occurred in 77% (n=48).

Grade 3/4 treatment-related AEs included neutropenia (60%), thrombocytopenia (60%), anemia (31%), leukopenia (6%), lymphopenia (6%), febrile neutropenia (6%), and infections (6%).

Twenty-one percent of patients had at least 1 treatment-related serious AE. The most frequent were febrile neutropenia (6%) and pneumonia (3%).

There were no treatment-related deaths.

Photo from EHA

STOCKHOLM—The alkylating peptide melflufen has demonstrated activity in patients with treatment-resistant multiple myeloma (MM).

In a phase 2 trial, melflufen plus dexamethasone produced an overall response rate (ORR) of 32.1% in MM patients who were refractory to pomalidomide and/or daratumumab and had failed treatment with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs).

Nearly all patients experienced an adverse event (AE) related to study treatment, and most of these were hematologic events.

These results, from the ongoing HORIZON trial, were presented at the 23rd Congress of the European Hematology Association (EHA) as abstract PF581.

The research was sponsored by Oncopeptides AB, the company developing melflufen.

“With an increasing number of patients with highly resistant myeloma, there is a real need for additional treatment options based on new mechanisms of action,” said study investigator Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“[Melflufen], a peptidase-enhanced compound, with its potent activity, manageable tolerability, and lack of shared resistance mechanisms with other modalities, is a promising molecule that is making encouraging progress in clinical development.”

Patients and treatment

The data presented at EHA include 62 patients. The data cut-off was May 10, 2018.

The patients had a median age of 62.5 (range, 41-82), 54% had high-risk cytogenetics, and 46% were ISS stage III. The patients had a median of 5.5 prior lines of therapy, and their median time since initial diagnosis was 6.1 years.

All patients were refractory to pomalidomide or daratumumab, 56% were refractory to both drugs, and 89% were double-refractory to IMiDs and PIs. Ninety-eight percent of patients had disease progression on or within 60 days of completing their last therapy.

Patients received melflufen at 40 mg (intravenously over 30 minutes) on day 1 of each 28-day cycle. They also received dexamethasone at 40 mg weekly. Patients were treated until disease progression, unacceptable toxicity, or withdrawal of consent.

At the data cutoff, 49 patients (79%) had completed at least 2 cycles of melflufen. The median number of cycles was 2 (range, 1-11).

Twenty-one patients (34%) were still receiving study treatment at the data cutoff. Reasons for discontinuation included disease progression (47%), AEs (15%), and physician decision (3%). One discontinuation was due to patient request.

Results

Fifty-six patients received at least 1 dose of melflufen and were evaluable for response.

The ORR was 32.1%, and the clinical benefit rate was 39.3%. ORR was defined as partial response (PR) or better, and clinical benefit rate was defined as minor response or better.

Two percent of patients had a complete response, 9% had a very good PR, 21% had a PR, and 7% had a minor response. Forty-five percent of patients had stable disease, and 16% progressed.

Subgroup analyses showed that response didn’t vary across refractory subsets, but it did vary according to the underlying disease and health status of the patient.

Treatment-related AEs occurred in 97% of all patients (60/62), and grade 3/4 treatment-related AEs occurred in 77% (n=48).

Grade 3/4 treatment-related AEs included neutropenia (60%), thrombocytopenia (60%), anemia (31%), leukopenia (6%), lymphopenia (6%), febrile neutropenia (6%), and infections (6%).

Twenty-one percent of patients had at least 1 treatment-related serious AE. The most frequent were febrile neutropenia (6%) and pneumonia (3%).

There were no treatment-related deaths.

Photo from EHA

STOCKHOLM—The alkylating peptide melflufen has demonstrated activity in patients with treatment-resistant multiple myeloma (MM).

In a phase 2 trial, melflufen plus dexamethasone produced an overall response rate (ORR) of 32.1% in MM patients who were refractory to pomalidomide and/or daratumumab and had failed treatment with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs).

Nearly all patients experienced an adverse event (AE) related to study treatment, and most of these were hematologic events.

These results, from the ongoing HORIZON trial, were presented at the 23rd Congress of the European Hematology Association (EHA) as abstract PF581.

The research was sponsored by Oncopeptides AB, the company developing melflufen.

“With an increasing number of patients with highly resistant myeloma, there is a real need for additional treatment options based on new mechanisms of action,” said study investigator Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“[Melflufen], a peptidase-enhanced compound, with its potent activity, manageable tolerability, and lack of shared resistance mechanisms with other modalities, is a promising molecule that is making encouraging progress in clinical development.”

Patients and treatment

The data presented at EHA include 62 patients. The data cut-off was May 10, 2018.

The patients had a median age of 62.5 (range, 41-82), 54% had high-risk cytogenetics, and 46% were ISS stage III. The patients had a median of 5.5 prior lines of therapy, and their median time since initial diagnosis was 6.1 years.

All patients were refractory to pomalidomide or daratumumab, 56% were refractory to both drugs, and 89% were double-refractory to IMiDs and PIs. Ninety-eight percent of patients had disease progression on or within 60 days of completing their last therapy.

Patients received melflufen at 40 mg (intravenously over 30 minutes) on day 1 of each 28-day cycle. They also received dexamethasone at 40 mg weekly. Patients were treated until disease progression, unacceptable toxicity, or withdrawal of consent.

At the data cutoff, 49 patients (79%) had completed at least 2 cycles of melflufen. The median number of cycles was 2 (range, 1-11).

Twenty-one patients (34%) were still receiving study treatment at the data cutoff. Reasons for discontinuation included disease progression (47%), AEs (15%), and physician decision (3%). One discontinuation was due to patient request.

Results

Fifty-six patients received at least 1 dose of melflufen and were evaluable for response.

The ORR was 32.1%, and the clinical benefit rate was 39.3%. ORR was defined as partial response (PR) or better, and clinical benefit rate was defined as minor response or better.

Two percent of patients had a complete response, 9% had a very good PR, 21% had a PR, and 7% had a minor response. Forty-five percent of patients had stable disease, and 16% progressed.

Subgroup analyses showed that response didn’t vary across refractory subsets, but it did vary according to the underlying disease and health status of the patient.

Treatment-related AEs occurred in 97% of all patients (60/62), and grade 3/4 treatment-related AEs occurred in 77% (n=48).

Grade 3/4 treatment-related AEs included neutropenia (60%), thrombocytopenia (60%), anemia (31%), leukopenia (6%), lymphopenia (6%), febrile neutropenia (6%), and infections (6%).

Twenty-one percent of patients had at least 1 treatment-related serious AE. The most frequent were febrile neutropenia (6%) and pneumonia (3%).

There were no treatment-related deaths.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

Photo courtesy of Roche

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of tocilizumab (RoActemra).

The recommendation is for tocilizumab to treat adults and pediatric patients age 2 and older who have severe or life-threatening cytokine release syndrome (CRS) induced by chimeric antigen receptor (CAR) T-cell therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

Tocilizumab is a humanized interleukin-6 receptor antagonist marketed by Roche Registration GmbH.

The drug is already approved by the European Commission to treat rheumatoid arthritis, active systemic juvenile idiopathic arthritis, and juvenile idiopathic polyarthritis.

The CHMP’s recommendation to expand the approved use of tocilizumab is supported by results from a retrospective analysis of data from clinical trials of CAR T-cell therapies in patients with hematologic malignancies.

For this analysis, researchers assessed 45 pediatric and adult patients treated with tocilizumab, with or without additional high-dose corticosteroids, for severe or life-threatening CRS.

Thirty-one patients (69%) achieved a response, defined as resolution of CRS within 14 days of the first dose of tocilizumab.

No more than 2 doses of tocilizumab were needed, and no drugs other than tocilizumab and corticosteroids were used for treatment.

No adverse reactions related to tocilizumab were reported.

Photo courtesy of Roche

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of tocilizumab (RoActemra).

The recommendation is for tocilizumab to treat adults and pediatric patients age 2 and older who have severe or life-threatening cytokine release syndrome (CRS) induced by chimeric antigen receptor (CAR) T-cell therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

Tocilizumab is a humanized interleukin-6 receptor antagonist marketed by Roche Registration GmbH.

The drug is already approved by the European Commission to treat rheumatoid arthritis, active systemic juvenile idiopathic arthritis, and juvenile idiopathic polyarthritis.

The CHMP’s recommendation to expand the approved use of tocilizumab is supported by results from a retrospective analysis of data from clinical trials of CAR T-cell therapies in patients with hematologic malignancies.

For this analysis, researchers assessed 45 pediatric and adult patients treated with tocilizumab, with or without additional high-dose corticosteroids, for severe or life-threatening CRS.

Thirty-one patients (69%) achieved a response, defined as resolution of CRS within 14 days of the first dose of tocilizumab.

No more than 2 doses of tocilizumab were needed, and no drugs other than tocilizumab and corticosteroids were used for treatment.

No adverse reactions related to tocilizumab were reported.

Photo courtesy of Roche

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of tocilizumab (RoActemra).

The recommendation is for tocilizumab to treat adults and pediatric patients age 2 and older who have severe or life-threatening cytokine release syndrome (CRS) induced by chimeric antigen receptor (CAR) T-cell therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

Tocilizumab is a humanized interleukin-6 receptor antagonist marketed by Roche Registration GmbH.

The drug is already approved by the European Commission to treat rheumatoid arthritis, active systemic juvenile idiopathic arthritis, and juvenile idiopathic polyarthritis.

The CHMP’s recommendation to expand the approved use of tocilizumab is supported by results from a retrospective analysis of data from clinical trials of CAR T-cell therapies in patients with hematologic malignancies.

For this analysis, researchers assessed 45 pediatric and adult patients treated with tocilizumab, with or without additional high-dose corticosteroids, for severe or life-threatening CRS.

Thirty-one patients (69%) achieved a response, defined as resolution of CRS within 14 days of the first dose of tocilizumab.

No more than 2 doses of tocilizumab were needed, and no drugs other than tocilizumab and corticosteroids were used for treatment.

No adverse reactions related to tocilizumab were reported.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – For patients with relapsed/refractory multiple myeloma previously exposed to lenalidomide, the combination of pomalidomide plus bortezomib and low‐dose dexamethasone (PVd) improved response and progression-free survival, results of the phase 3 OPTIMISMM trial showed.

Risk of disease progression or death was reduced by 39%, compared with bortezomib and low-dose dexamethasone alone (Vd), among patients in the trial, of whom approximately 70% were lenalidomide refractory, reported investigator Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston.

The improvements in efficacy seen with the PVd regimen were more pronounced in patients with only one prior line of therapy, and overall, the safety profile of the triplet regimen was consistent with known toxicities of each individual agent, Dr. Richardson reported.

Together, those results “would seem to support the use of this triplet [therapy] in first relapse in patients with relapsed/refractory myeloma and prior exposure to lenalidomide,” he said at the annual meeting of the American Society of Clinical Oncology.

“This study, importantly, evaluated a clinically relevant patient population and a growing patient population who receive upfront lenalidomide and maintenance in that setting and for whom lenalidomide is no longer a viable treatment option,” Dr. Richardson added.

Lenalidomide has become a mainstay of upfront myeloma treatment, and the Food and Drug Administration recently gave approval to lenalidomide as maintenance after autologous hematopoietic stem cell transplantation. Accordingly, it’s important to understand the benefits of triplet therapies in patients progressing on lenalidomide therapy and in whom lenalidomide is no longer a treatment option, Dr. Richardson said.

Pomalidomide, a potent oral immunomodulatory agent, is already approved for relapsed/refractory myeloma after two or more previous therapies that include lenalidomide and a proteasome inhibitor in patients who progress on or within 60 days of treatment.

In the OPTIMISMM trial, 559 patients who had received prior therapy, including at least two cycles of lenalidomide, were randomized to receive either PVd or Vd until disease progression or unacceptable toxicity.

Median progression-free survival was 11.20 months for PVd versus 7.10 months for Vd (hazard ratio, 0.61; 95% confidence interval, 0.49-0.77; P less than .0001).

Progression-free survival results were “even more encouraging” in the subset of patients with only one prior line of therapy, Dr. Richardson said, reporting a median of 20.73 months for PVd versus 11.63 for Vd (HR, 0.54; 95% CI, 0.36-0.82; P = .0027).

The overall response rate was 82.2% for PVd versus 50.0% for Vd (P less than .001). In patients with only one prior line of therapy, the overall response rate was 90.1% and 54.8% for PVd and Vd, respectively (P less than .001).

The progression-free survival advantage occurred regardless of whether patients were refractory to lenalidomide, Dr. Richardson added. Median progression-free survival for PVd versus Vd was 9.53 and 5.59 months, respectively, in the lenalidomide-refractory patients (P less than .001) and 22.01 versus 11.63 months in non–lenalidomide refractory patients (P less than .001).

The side effect profile of PVd was “very much as expected,” with more neutropenia seen with the PVd than with Vd, though rates of febrile neutropenia were low, Dr. Richardson said. Likewise, the rate of infection was higher in the triplet arm, but it was generally manageable, he added.

Deep vein thrombosis and pulmonary embolism rates were low in both arms, as were the rates of secondary primary malignancies. Analysis of minimal residual disease and quality of life are ongoing.

PVd could “arguably be now an important treatment platform for future directions in combination with other strategies,” Dr. Richardson said.

The study was supported by Celgene. Dr. Richardson reported advisory board work for Celgene, Novartis, Oncopeptides, Janssen, Amgen, and Takeda, and research funding from Bristol-Myers Squibb, Celgene, and Takeda.

SOURCE: Richardson PG et al. ASCO 2018, Abstract 8001.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

Bristol-Myers Squibb

STOCKHOLM—Adding elotuzumab (E) to treatment with pomalidomide (P) and low-dose dexamethasone (d) can produce “clinically meaningful” results in patients with relapsed/refractory multiple myeloma (MM), according to an investigator for the ELOQUENT-3 trial.

In this phase 2 trial, patients who received EPd had double the overall response rate (ORR) and median progression-free survival (PFS) of patients who received Pd.

Additionally, adverse events (AEs) were comparable between the treatment arms.

Meletios Dimopoulos, MD, of National and Kapodistrian University of Athens in Greece, presented these results as a late-breaking abstract (LB2606) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Bristol-Myers Squibb.

The ELOQUENT-3 trial enrolled MM patients who had refractory or relapsed and refractory MM. They had to have received lenalidomide and a proteasome inhibitor (PI).

The patients were randomized to receive EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.

Pomalidomide was given orally at 4 mg on days 1 to 21 of each cycle. In the Pd arm, dexamethasone was given as a 20 mg (for patients older than 75) or 40 mg (75 and younger) tablet weekly.

In the EPd arm, dexamethasone was split between oral (8 mg, 20 mg, or 40 mg tablets) and intravenous doses (8 mg or 28 mg).

Elotuzumab was given at 10 mg/kg intravenously weekly for the first 2 cycles and 20 mg/kg monthly from cycle 3 on.

Patient characteristics

The patients’ median age was 69 (range, 43-81) in the EPd arm and 66 (range, 36-81) in the Pd arm. They were a median of 4.8 years (EPd) or 4.4 years (Pd) from diagnosis.

The median number of prior therapies was 3 (range, 2-8) in both groups.

Ninety percent of patients in the EPd arm and 84% of those in the Pd arm were refractory to lenalidomide. Seventy-eight percent and 82%, respectively, were refractory to a PI. And 68% and 72%, respectively, were refractory to both lenalidomide and a PI.

Treatment duration

Dr Dimopoulos noted that twice as many patients remained on treatment with EPd compared to Pd at the time of database lock (February 21, 2018). Forty percent of EPd patients (n=24) and 20% of Pd patients (n=11) were still on treatment at that time.

Patients’ primary reason for treatment discontinuation was disease progression—43% of EPd recipients and 56% of Pd recipients. Two percent of EPd recipients and 4% of Pd recipients withdrew due to treatment-related toxicity. Four percent of patients in the Pd arm (and none in the EPd arm) withdrew due to maximum clinical benefit.

The median number of treatment cycles was 9 (range, 4-13) in the EPd arm and 5 (range, 3-10) in the Pd arm.

Efficacy

The ORR was 53% in the EPd arm and 26% in the Pd arm. The odds ratio was 3.25 (P=0.0029).

Eight percent of patients in the EPd arm had a complete response or stringent complete response, as did 2% of patients in the Pd arm.

The median duration of response was 8.3 months in the Pd arm and has not been reached in the EPd arm.

“Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” Dr Dimopoulos said.

The median PFS was 10.3 months with EPd and 4.7 months with Pd (hazard ratio=0.54, P=0.0078).

Although overall survival data are not yet mature, there was a trend favoring EPd over Pd (hazard ratio=0.62). There were 13 deaths in the EPd arm and 18 deaths in the Pd arm.

Safety

Dr Dimopoulos said AEs were comparable between the treatment arms. He pointed out that neutropenia was less common with EPd compared to Pd, despite similar pomalidomide dose intensity. And exposure-adjusted hematologic AEs and infections were lower with EPd than with Pd.

Ninety-seven percent of patients in the EPd arm and 95% in the Pd arm had at least 1 AE.

Grade 3-4 nonhematologic AEs (in the EPd and Pd arms, respectively) included constipation (2% and 0%), hyperglycemia (8% and 7%), bone pain (3% and 0%), dyspnea (3% and 2%), fatigue (0% and 4%), respiratory tract infection (0% and 2%), and upper respiratory tract infection (0% and 2%).

Grade 3-4 hematologic AEs (in the EPd and Pd arms, respectively) included anemia (10% and 20%), neutropenia (13% and 27%), thrombocytopenia (8% and 5%), and lymphopenia (8% and 2%).

Grade 3-4 AEs of special interest (in the EPd and Pd arms, respectively) included infections (13% and 22%), vascular disorders (3% and 0%), cardiac disorders (7% and 4%), and neoplasms (2% and 11%).

There were 5 grade 5 AEs in the EPd arm and 8 in the Pd arm.

In the EPd arm, grade 5 AEs included infection (n=3), cardiac failure, and general physical health deterioration.

In the Pd arm, grade 5 AEs included malignant neoplasm progression (n=4), infection, multiple organ failure and infection, myocardial infarction, and plasma cell myeloma.

Bristol-Myers Squibb

STOCKHOLM—Adding elotuzumab (E) to treatment with pomalidomide (P) and low-dose dexamethasone (d) can produce “clinically meaningful” results in patients with relapsed/refractory multiple myeloma (MM), according to an investigator for the ELOQUENT-3 trial.

In this phase 2 trial, patients who received EPd had double the overall response rate (ORR) and median progression-free survival (PFS) of patients who received Pd.

Additionally, adverse events (AEs) were comparable between the treatment arms.

Meletios Dimopoulos, MD, of National and Kapodistrian University of Athens in Greece, presented these results as a late-breaking abstract (LB2606) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Bristol-Myers Squibb.

The ELOQUENT-3 trial enrolled MM patients who had refractory or relapsed and refractory MM. They had to have received lenalidomide and a proteasome inhibitor (PI).

The patients were randomized to receive EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.

Pomalidomide was given orally at 4 mg on days 1 to 21 of each cycle. In the Pd arm, dexamethasone was given as a 20 mg (for patients older than 75) or 40 mg (75 and younger) tablet weekly.

In the EPd arm, dexamethasone was split between oral (8 mg, 20 mg, or 40 mg tablets) and intravenous doses (8 mg or 28 mg).

Elotuzumab was given at 10 mg/kg intravenously weekly for the first 2 cycles and 20 mg/kg monthly from cycle 3 on.

Patient characteristics

The patients’ median age was 69 (range, 43-81) in the EPd arm and 66 (range, 36-81) in the Pd arm. They were a median of 4.8 years (EPd) or 4.4 years (Pd) from diagnosis.

The median number of prior therapies was 3 (range, 2-8) in both groups.

Ninety percent of patients in the EPd arm and 84% of those in the Pd arm were refractory to lenalidomide. Seventy-eight percent and 82%, respectively, were refractory to a PI. And 68% and 72%, respectively, were refractory to both lenalidomide and a PI.

Treatment duration

Dr Dimopoulos noted that twice as many patients remained on treatment with EPd compared to Pd at the time of database lock (February 21, 2018). Forty percent of EPd patients (n=24) and 20% of Pd patients (n=11) were still on treatment at that time.

Patients’ primary reason for treatment discontinuation was disease progression—43% of EPd recipients and 56% of Pd recipients. Two percent of EPd recipients and 4% of Pd recipients withdrew due to treatment-related toxicity. Four percent of patients in the Pd arm (and none in the EPd arm) withdrew due to maximum clinical benefit.

The median number of treatment cycles was 9 (range, 4-13) in the EPd arm and 5 (range, 3-10) in the Pd arm.

Efficacy

The ORR was 53% in the EPd arm and 26% in the Pd arm. The odds ratio was 3.25 (P=0.0029).

Eight percent of patients in the EPd arm had a complete response or stringent complete response, as did 2% of patients in the Pd arm.

The median duration of response was 8.3 months in the Pd arm and has not been reached in the EPd arm.

“Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” Dr Dimopoulos said.

The median PFS was 10.3 months with EPd and 4.7 months with Pd (hazard ratio=0.54, P=0.0078).

Although overall survival data are not yet mature, there was a trend favoring EPd over Pd (hazard ratio=0.62). There were 13 deaths in the EPd arm and 18 deaths in the Pd arm.

Safety

Dr Dimopoulos said AEs were comparable between the treatment arms. He pointed out that neutropenia was less common with EPd compared to Pd, despite similar pomalidomide dose intensity. And exposure-adjusted hematologic AEs and infections were lower with EPd than with Pd.

Ninety-seven percent of patients in the EPd arm and 95% in the Pd arm had at least 1 AE.

Grade 3-4 nonhematologic AEs (in the EPd and Pd arms, respectively) included constipation (2% and 0%), hyperglycemia (8% and 7%), bone pain (3% and 0%), dyspnea (3% and 2%), fatigue (0% and 4%), respiratory tract infection (0% and 2%), and upper respiratory tract infection (0% and 2%).

Grade 3-4 hematologic AEs (in the EPd and Pd arms, respectively) included anemia (10% and 20%), neutropenia (13% and 27%), thrombocytopenia (8% and 5%), and lymphopenia (8% and 2%).

Grade 3-4 AEs of special interest (in the EPd and Pd arms, respectively) included infections (13% and 22%), vascular disorders (3% and 0%), cardiac disorders (7% and 4%), and neoplasms (2% and 11%).

There were 5 grade 5 AEs in the EPd arm and 8 in the Pd arm.

In the EPd arm, grade 5 AEs included infection (n=3), cardiac failure, and general physical health deterioration.

In the Pd arm, grade 5 AEs included malignant neoplasm progression (n=4), infection, multiple organ failure and infection, myocardial infarction, and plasma cell myeloma.

Bristol-Myers Squibb

STOCKHOLM—Adding elotuzumab (E) to treatment with pomalidomide (P) and low-dose dexamethasone (d) can produce “clinically meaningful” results in patients with relapsed/refractory multiple myeloma (MM), according to an investigator for the ELOQUENT-3 trial.

In this phase 2 trial, patients who received EPd had double the overall response rate (ORR) and median progression-free survival (PFS) of patients who received Pd.

Additionally, adverse events (AEs) were comparable between the treatment arms.

Meletios Dimopoulos, MD, of National and Kapodistrian University of Athens in Greece, presented these results as a late-breaking abstract (LB2606) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Bristol-Myers Squibb.

The ELOQUENT-3 trial enrolled MM patients who had refractory or relapsed and refractory MM. They had to have received lenalidomide and a proteasome inhibitor (PI).

The patients were randomized to receive EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.

Pomalidomide was given orally at 4 mg on days 1 to 21 of each cycle. In the Pd arm, dexamethasone was given as a 20 mg (for patients older than 75) or 40 mg (75 and younger) tablet weekly.

In the EPd arm, dexamethasone was split between oral (8 mg, 20 mg, or 40 mg tablets) and intravenous doses (8 mg or 28 mg).

Elotuzumab was given at 10 mg/kg intravenously weekly for the first 2 cycles and 20 mg/kg monthly from cycle 3 on.

Patient characteristics

The patients’ median age was 69 (range, 43-81) in the EPd arm and 66 (range, 36-81) in the Pd arm. They were a median of 4.8 years (EPd) or 4.4 years (Pd) from diagnosis.

The median number of prior therapies was 3 (range, 2-8) in both groups.

Ninety percent of patients in the EPd arm and 84% of those in the Pd arm were refractory to lenalidomide. Seventy-eight percent and 82%, respectively, were refractory to a PI. And 68% and 72%, respectively, were refractory to both lenalidomide and a PI.

Treatment duration

Dr Dimopoulos noted that twice as many patients remained on treatment with EPd compared to Pd at the time of database lock (February 21, 2018). Forty percent of EPd patients (n=24) and 20% of Pd patients (n=11) were still on treatment at that time.

Patients’ primary reason for treatment discontinuation was disease progression—43% of EPd recipients and 56% of Pd recipients. Two percent of EPd recipients and 4% of Pd recipients withdrew due to treatment-related toxicity. Four percent of patients in the Pd arm (and none in the EPd arm) withdrew due to maximum clinical benefit.

The median number of treatment cycles was 9 (range, 4-13) in the EPd arm and 5 (range, 3-10) in the Pd arm.

Efficacy

The ORR was 53% in the EPd arm and 26% in the Pd arm. The odds ratio was 3.25 (P=0.0029).

Eight percent of patients in the EPd arm had a complete response or stringent complete response, as did 2% of patients in the Pd arm.

The median duration of response was 8.3 months in the Pd arm and has not been reached in the EPd arm.

“Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” Dr Dimopoulos said.

The median PFS was 10.3 months with EPd and 4.7 months with Pd (hazard ratio=0.54, P=0.0078).

Although overall survival data are not yet mature, there was a trend favoring EPd over Pd (hazard ratio=0.62). There were 13 deaths in the EPd arm and 18 deaths in the Pd arm.

Safety

Dr Dimopoulos said AEs were comparable between the treatment arms. He pointed out that neutropenia was less common with EPd compared to Pd, despite similar pomalidomide dose intensity. And exposure-adjusted hematologic AEs and infections were lower with EPd than with Pd.

Ninety-seven percent of patients in the EPd arm and 95% in the Pd arm had at least 1 AE.

Grade 3-4 nonhematologic AEs (in the EPd and Pd arms, respectively) included constipation (2% and 0%), hyperglycemia (8% and 7%), bone pain (3% and 0%), dyspnea (3% and 2%), fatigue (0% and 4%), respiratory tract infection (0% and 2%), and upper respiratory tract infection (0% and 2%).

Grade 3-4 hematologic AEs (in the EPd and Pd arms, respectively) included anemia (10% and 20%), neutropenia (13% and 27%), thrombocytopenia (8% and 5%), and lymphopenia (8% and 2%).

Grade 3-4 AEs of special interest (in the EPd and Pd arms, respectively) included infections (13% and 22%), vascular disorders (3% and 0%), cardiac disorders (7% and 4%), and neoplasms (2% and 11%).

There were 5 grade 5 AEs in the EPd arm and 8 in the Pd arm.

In the EPd arm, grade 5 AEs included infection (n=3), cardiac failure, and general physical health deterioration.

In the Pd arm, grade 5 AEs included malignant neoplasm progression (n=4), infection, multiple organ failure and infection, myocardial infarction, and plasma cell myeloma.

Photo by Andrew D. Bowser

CHICAGO—bb2121, the anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, induced deep and durable ongoing responses in heavily pretreated multiple myeloma (MM) patients, updated results of a phase 1 study show.

At active doses (≥150 x 10⁸ CAR+ T cells), the B-cell maturation antigen (BCMA)-targeted therapy produced an overall response rate of 95.5%, including a 50% rate of complete response (CR) or stringent CR, with a median duration of response of 10.8 months.

Median progression-free survival (PFS) was 11.8 months in the dose-escalation cohort.

Noopur S. Raje, MD, of the Massachusetts General Hospital Cancer Center in Boston, reported these results at the 2018 ASCO Annual Meeting (abstract 8007*). The study is sponsored by Celgene Corporation and bluebird bio.

To date, bb2121 has been manageable for patients at doses as high as 800 x 10⁸ CAR T cells, Dr Raje noted.

She updated the findings of CRB-401 (NCT02658929), which included 43 patients with relapsed/refractory MM, including 21 in a dose-escalation (DE) cohort and 22 in a dose-expansion (Exp) cohort.

Patients received one infusion of bb2121 anti-BCMA CAR T cells after a lymphodepleting conditioning regimen including fludarabine and cyclophosphamide.

Patients were a median age of 58 (range, 37 – 74) and 65 (range, 44 – 75) in the DE and Exp cohorts, respectively.

Eight patients (38%) in the DE cohort and 9 (41%) in the Exp cohort had high-risk cytogenetics and had received a median of 7 (range, 3 – 14) and 8 (range, 3 – 23) prior regimens, respectively.

All patients in the DE cohort and 86% in the Exp cohort had a prior autologous stem cell transplant (ASCT), and 29% and 23% in each cohort, respectively, had more than one ASCT.

Results

Patients in the DE cohort had a median PFS of 11.8 months at active doses.

All 16 responding patients who were evaluable for minimal residual disease (MRD) achieved MRD negativity and had a median PFS of 17.7 months.

The investigators observed a dose-response relationship across the active dose ranges and higher peak CAR T expansion in responding patients compared with those who did not respond.

The investigators also noted that the tumor response was independent of tumor BCMA expression.

bb2121 persisted for 6 months or longer in 44% of responding patients.

“This should be tested a little bit earlier now, because what we’ve done here is show the proof of concept, and really treated these very end-stage myeloma patients,” Dr Raje observed.

Adverse events of interest

“We found that this product is extremely well tolerated,” Dr Raje said. “We saw, certainly, cytokine release syndrome (CRS) in over 60% of patients, but most of the CRS was managed, and it was grade 1 and 2 with very little grade 3 CRS. [W]e just had 1 patient with grade 4 neurotoxicity who is now completely recovered.”

The 2 grade 3 CRS events observed in this study resolved in 24 hours, Dr Raje noted.

Infused patients (n=43) also experienced neutropenia (81%), thrombocytopenia (61%), and anemia (56%).

Thirty-one of 40 patients (78%) recovered their absolute neutrophil count to 1000/μL or greater by day 32, and 22 of 40 (55%) patients recovered their platelet counts to 50,000/μL or greater by day 32.

Commentary

BCMA is the “latest promising target” in MM, said Parameswaran Hari, MD, of the Medical College of Wisconsin in Milwaukee, and this bb2121 data represents the largest and most mature experience with the CAR T approach in the disease.

However, patients are still relapsing, and the meaning of MRD negativity is unclear in this setting, Dr Parameswaran said in a presentation referencing the results of the study.

“Unfortunately, this is not yet a cure, so I’m going advise my patients who are in stringent CR and on maintenance not to go for CAR T cells unless they relapse,” he said.

An ongoing global trial of bb2121, known as KarMMa, is open for enrollment in North America and Europe, and additional studies are planned in earlier lines of myeloma.

*Data presented at the meeting differ from the abstract. 

Photo by Andrew D. Bowser

CHICAGO—bb2121, the anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, induced deep and durable ongoing responses in heavily pretreated multiple myeloma (MM) patients, updated results of a phase 1 study show.

At active doses (≥150 x 10⁸ CAR+ T cells), the B-cell maturation antigen (BCMA)-targeted therapy produced an overall response rate of 95.5%, including a 50% rate of complete response (CR) or stringent CR, with a median duration of response of 10.8 months.

Median progression-free survival (PFS) was 11.8 months in the dose-escalation cohort.

Noopur S. Raje, MD, of the Massachusetts General Hospital Cancer Center in Boston, reported these results at the 2018 ASCO Annual Meeting (abstract 8007*). The study is sponsored by Celgene Corporation and bluebird bio.

To date, bb2121 has been manageable for patients at doses as high as 800 x 10⁸ CAR T cells, Dr Raje noted.

She updated the findings of CRB-401 (NCT02658929), which included 43 patients with relapsed/refractory MM, including 21 in a dose-escalation (DE) cohort and 22 in a dose-expansion (Exp) cohort.

Patients received one infusion of bb2121 anti-BCMA CAR T cells after a lymphodepleting conditioning regimen including fludarabine and cyclophosphamide.

Patients were a median age of 58 (range, 37 – 74) and 65 (range, 44 – 75) in the DE and Exp cohorts, respectively.

Eight patients (38%) in the DE cohort and 9 (41%) in the Exp cohort had high-risk cytogenetics and had received a median of 7 (range, 3 – 14) and 8 (range, 3 – 23) prior regimens, respectively.

All patients in the DE cohort and 86% in the Exp cohort had a prior autologous stem cell transplant (ASCT), and 29% and 23% in each cohort, respectively, had more than one ASCT.

Results

Patients in the DE cohort had a median PFS of 11.8 months at active doses.

All 16 responding patients who were evaluable for minimal residual disease (MRD) achieved MRD negativity and had a median PFS of 17.7 months.

The investigators observed a dose-response relationship across the active dose ranges and higher peak CAR T expansion in responding patients compared with those who did not respond.

The investigators also noted that the tumor response was independent of tumor BCMA expression.

bb2121 persisted for 6 months or longer in 44% of responding patients.

“This should be tested a little bit earlier now, because what we’ve done here is show the proof of concept, and really treated these very end-stage myeloma patients,” Dr Raje observed.

Adverse events of interest

“We found that this product is extremely well tolerated,” Dr Raje said. “We saw, certainly, cytokine release syndrome (CRS) in over 60% of patients, but most of the CRS was managed, and it was grade 1 and 2 with very little grade 3 CRS. [W]e just had 1 patient with grade 4 neurotoxicity who is now completely recovered.”

The 2 grade 3 CRS events observed in this study resolved in 24 hours, Dr Raje noted.

Infused patients (n=43) also experienced neutropenia (81%), thrombocytopenia (61%), and anemia (56%).

Thirty-one of 40 patients (78%) recovered their absolute neutrophil count to 1000/μL or greater by day 32, and 22 of 40 (55%) patients recovered their platelet counts to 50,000/μL or greater by day 32.

Commentary

BCMA is the “latest promising target” in MM, said Parameswaran Hari, MD, of the Medical College of Wisconsin in Milwaukee, and this bb2121 data represents the largest and most mature experience with the CAR T approach in the disease.

However, patients are still relapsing, and the meaning of MRD negativity is unclear in this setting, Dr Parameswaran said in a presentation referencing the results of the study.

“Unfortunately, this is not yet a cure, so I’m going advise my patients who are in stringent CR and on maintenance not to go for CAR T cells unless they relapse,” he said.

An ongoing global trial of bb2121, known as KarMMa, is open for enrollment in North America and Europe, and additional studies are planned in earlier lines of myeloma.

*Data presented at the meeting differ from the abstract. 

Photo by Andrew D. Bowser

CHICAGO—bb2121, the anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, induced deep and durable ongoing responses in heavily pretreated multiple myeloma (MM) patients, updated results of a phase 1 study show.

At active doses (≥150 x 10⁸ CAR+ T cells), the B-cell maturation antigen (BCMA)-targeted therapy produced an overall response rate of 95.5%, including a 50% rate of complete response (CR) or stringent CR, with a median duration of response of 10.8 months.

Median progression-free survival (PFS) was 11.8 months in the dose-escalation cohort.

Noopur S. Raje, MD, of the Massachusetts General Hospital Cancer Center in Boston, reported these results at the 2018 ASCO Annual Meeting (abstract 8007*). The study is sponsored by Celgene Corporation and bluebird bio.

To date, bb2121 has been manageable for patients at doses as high as 800 x 10⁸ CAR T cells, Dr Raje noted.

She updated the findings of CRB-401 (NCT02658929), which included 43 patients with relapsed/refractory MM, including 21 in a dose-escalation (DE) cohort and 22 in a dose-expansion (Exp) cohort.

Patients received one infusion of bb2121 anti-BCMA CAR T cells after a lymphodepleting conditioning regimen including fludarabine and cyclophosphamide.

Patients were a median age of 58 (range, 37 – 74) and 65 (range, 44 – 75) in the DE and Exp cohorts, respectively.

Eight patients (38%) in the DE cohort and 9 (41%) in the Exp cohort had high-risk cytogenetics and had received a median of 7 (range, 3 – 14) and 8 (range, 3 – 23) prior regimens, respectively.

All patients in the DE cohort and 86% in the Exp cohort had a prior autologous stem cell transplant (ASCT), and 29% and 23% in each cohort, respectively, had more than one ASCT.

Results

Patients in the DE cohort had a median PFS of 11.8 months at active doses.

All 16 responding patients who were evaluable for minimal residual disease (MRD) achieved MRD negativity and had a median PFS of 17.7 months.

The investigators observed a dose-response relationship across the active dose ranges and higher peak CAR T expansion in responding patients compared with those who did not respond.

The investigators also noted that the tumor response was independent of tumor BCMA expression.

bb2121 persisted for 6 months or longer in 44% of responding patients.

“This should be tested a little bit earlier now, because what we’ve done here is show the proof of concept, and really treated these very end-stage myeloma patients,” Dr Raje observed.

Adverse events of interest

“We found that this product is extremely well tolerated,” Dr Raje said. “We saw, certainly, cytokine release syndrome (CRS) in over 60% of patients, but most of the CRS was managed, and it was grade 1 and 2 with very little grade 3 CRS. [W]e just had 1 patient with grade 4 neurotoxicity who is now completely recovered.”

The 2 grade 3 CRS events observed in this study resolved in 24 hours, Dr Raje noted.

Infused patients (n=43) also experienced neutropenia (81%), thrombocytopenia (61%), and anemia (56%).

Thirty-one of 40 patients (78%) recovered their absolute neutrophil count to 1000/μL or greater by day 32, and 22 of 40 (55%) patients recovered their platelet counts to 50,000/μL or greater by day 32.

Commentary

BCMA is the “latest promising target” in MM, said Parameswaran Hari, MD, of the Medical College of Wisconsin in Milwaukee, and this bb2121 data represents the largest and most mature experience with the CAR T approach in the disease.

However, patients are still relapsing, and the meaning of MRD negativity is unclear in this setting, Dr Parameswaran said in a presentation referencing the results of the study.

“Unfortunately, this is not yet a cure, so I’m going advise my patients who are in stringent CR and on maintenance not to go for CAR T cells unless they relapse,” he said.

An ongoing global trial of bb2121, known as KarMMa, is open for enrollment in North America and Europe, and additional studies are planned in earlier lines of myeloma.

*Data presented at the meeting differ from the abstract. 

©ASCO/Scott Morgan 2018

CHICAGO—The addition of pomalidomide to bortezomib and low‐dose dexamethasone (PVd) significantly improves progression-free survival (PFS) in lenalidomide-exposed patients with relapsed or refractory (R/R) multiple myeloma (MM), a new study reveals.

Up until now, pomalidomide and dexamethasone (Pd) had been the only therapy investigated exclusively after lenalidomide therapy, according to Paul G. Richardson, MD.

Now, he said, “a triple combination of PVd demonstrated promising activity in early phase clinical trials of lenalidomide-refractory patients.”

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented the findings of the phase 3 OPTIMISMM trial (abstract 8001) at the 2018 ASCO Annual Meeting.

The oral immunomodulatory agent pomalidomide, a standard-of-care treatment in R/R MM, has demonstrated synergistic anti-myeloma activity with dexamethasone and proteasome inhibitors.

A combination of pomalidomide and dexamethasone is indicated for MM patients after 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

“Lenalidomide is an established therapy in newly diagnosed multiple myeloma,” Dr Richardson explained. “Therefore, patients for whom lenalidomide is no longer a treatment option represent a clinically relevant population with unmet need.”

Phase 3 OPTIMISMM trial (NCT01734928)

Dr Richardson reported the final PFS and safety data from the first phase 3 pomalidomide triplet trial comparing PVd against bortezomib and dexamethasone (Vd) in an entirely post-lenalidomide treated population.

The 559 patients had 1 to 3 prior lines of therapy and 2 or more cycles of prior lenalidomide. They were randomized to receive PVd (281 patients, median age 67 years) or Vd (278 patients, median age 68 years).

In 21-day cycles, patients received pomalidomide 4 mg per day on days 1-14 (PVd arm only); bortezomib 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1-8 and on day 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg per day (10 mg for those over age 75) on the days of and after bortezomib.

The primary endpoint was PFS.

Results

After a median follow-up of 16 months, “PVd reduced the risk of progression or death by 39% compared with Vd,” Dr Richardson said.

Median PFS was 11.2 months in the PVd group and 7.1 months in the Vd group. Overall survival data are not mature.

The overall response rate was significantly higher with PVd (82.2%) vs Vd (50%).

And the overall response rate was even higher in patients with only 1 prior line of therapy (90.1% vs 54.8%, respectively).

“PVd led to deeper responses with higher stringent complete response/complete response and more very good partial responses than Vd,” Dr Richardson noted.

“PFS was improved with PVd vs Vd across patient subgroups and regardless of lenalidomide refractoriness. The PFS benefit with PVd was maintained through the next line of therapy.”

He reported longer treatment duration and exposure with PVd compared with Vd.

Safety

The safety profile was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone, he said.

Most common grade 3/4 treatment-emergent adverse events were higher with PVd than Vd, including neutropenia (42% vs 9%) and infections (31% vs 18%).

In conclusion, Dr Richardson said, “These results support the use of PVd in first relapse in patients with relapsed/refractory multiple myeloma and prior exposure to lenalidomide.”

Future analyses of the data will include correlatives, minimal residual disease, and quality of life, he said.

The trial was sponsored by Celgene. 

©ASCO/Scott Morgan 2018

CHICAGO—The addition of pomalidomide to bortezomib and low‐dose dexamethasone (PVd) significantly improves progression-free survival (PFS) in lenalidomide-exposed patients with relapsed or refractory (R/R) multiple myeloma (MM), a new study reveals.

Up until now, pomalidomide and dexamethasone (Pd) had been the only therapy investigated exclusively after lenalidomide therapy, according to Paul G. Richardson, MD.

Now, he said, “a triple combination of PVd demonstrated promising activity in early phase clinical trials of lenalidomide-refractory patients.”

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented the findings of the phase 3 OPTIMISMM trial (abstract 8001) at the 2018 ASCO Annual Meeting.

The oral immunomodulatory agent pomalidomide, a standard-of-care treatment in R/R MM, has demonstrated synergistic anti-myeloma activity with dexamethasone and proteasome inhibitors.

A combination of pomalidomide and dexamethasone is indicated for MM patients after 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

“Lenalidomide is an established therapy in newly diagnosed multiple myeloma,” Dr Richardson explained. “Therefore, patients for whom lenalidomide is no longer a treatment option represent a clinically relevant population with unmet need.”

Phase 3 OPTIMISMM trial (NCT01734928)

Dr Richardson reported the final PFS and safety data from the first phase 3 pomalidomide triplet trial comparing PVd against bortezomib and dexamethasone (Vd) in an entirely post-lenalidomide treated population.

The 559 patients had 1 to 3 prior lines of therapy and 2 or more cycles of prior lenalidomide. They were randomized to receive PVd (281 patients, median age 67 years) or Vd (278 patients, median age 68 years).

In 21-day cycles, patients received pomalidomide 4 mg per day on days 1-14 (PVd arm only); bortezomib 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1-8 and on day 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg per day (10 mg for those over age 75) on the days of and after bortezomib.

The primary endpoint was PFS.

Results

After a median follow-up of 16 months, “PVd reduced the risk of progression or death by 39% compared with Vd,” Dr Richardson said.

Median PFS was 11.2 months in the PVd group and 7.1 months in the Vd group. Overall survival data are not mature.

The overall response rate was significantly higher with PVd (82.2%) vs Vd (50%).

And the overall response rate was even higher in patients with only 1 prior line of therapy (90.1% vs 54.8%, respectively).

“PVd led to deeper responses with higher stringent complete response/complete response and more very good partial responses than Vd,” Dr Richardson noted.

“PFS was improved with PVd vs Vd across patient subgroups and regardless of lenalidomide refractoriness. The PFS benefit with PVd was maintained through the next line of therapy.”

He reported longer treatment duration and exposure with PVd compared with Vd.

Safety

The safety profile was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone, he said.

Most common grade 3/4 treatment-emergent adverse events were higher with PVd than Vd, including neutropenia (42% vs 9%) and infections (31% vs 18%).

In conclusion, Dr Richardson said, “These results support the use of PVd in first relapse in patients with relapsed/refractory multiple myeloma and prior exposure to lenalidomide.”

Future analyses of the data will include correlatives, minimal residual disease, and quality of life, he said.

The trial was sponsored by Celgene. 

©ASCO/Scott Morgan 2018

CHICAGO—The addition of pomalidomide to bortezomib and low‐dose dexamethasone (PVd) significantly improves progression-free survival (PFS) in lenalidomide-exposed patients with relapsed or refractory (R/R) multiple myeloma (MM), a new study reveals.

Up until now, pomalidomide and dexamethasone (Pd) had been the only therapy investigated exclusively after lenalidomide therapy, according to Paul G. Richardson, MD.

Now, he said, “a triple combination of PVd demonstrated promising activity in early phase clinical trials of lenalidomide-refractory patients.”

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented the findings of the phase 3 OPTIMISMM trial (abstract 8001) at the 2018 ASCO Annual Meeting.

The oral immunomodulatory agent pomalidomide, a standard-of-care treatment in R/R MM, has demonstrated synergistic anti-myeloma activity with dexamethasone and proteasome inhibitors.

A combination of pomalidomide and dexamethasone is indicated for MM patients after 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

“Lenalidomide is an established therapy in newly diagnosed multiple myeloma,” Dr Richardson explained. “Therefore, patients for whom lenalidomide is no longer a treatment option represent a clinically relevant population with unmet need.”

Phase 3 OPTIMISMM trial (NCT01734928)

Dr Richardson reported the final PFS and safety data from the first phase 3 pomalidomide triplet trial comparing PVd against bortezomib and dexamethasone (Vd) in an entirely post-lenalidomide treated population.

The 559 patients had 1 to 3 prior lines of therapy and 2 or more cycles of prior lenalidomide. They were randomized to receive PVd (281 patients, median age 67 years) or Vd (278 patients, median age 68 years).

In 21-day cycles, patients received pomalidomide 4 mg per day on days 1-14 (PVd arm only); bortezomib 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1-8 and on day 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg per day (10 mg for those over age 75) on the days of and after bortezomib.

The primary endpoint was PFS.

Results

After a median follow-up of 16 months, “PVd reduced the risk of progression or death by 39% compared with Vd,” Dr Richardson said.

Median PFS was 11.2 months in the PVd group and 7.1 months in the Vd group. Overall survival data are not mature.

The overall response rate was significantly higher with PVd (82.2%) vs Vd (50%).

And the overall response rate was even higher in patients with only 1 prior line of therapy (90.1% vs 54.8%, respectively).

“PVd led to deeper responses with higher stringent complete response/complete response and more very good partial responses than Vd,” Dr Richardson noted.

“PFS was improved with PVd vs Vd across patient subgroups and regardless of lenalidomide refractoriness. The PFS benefit with PVd was maintained through the next line of therapy.”

He reported longer treatment duration and exposure with PVd compared with Vd.

Safety

The safety profile was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone, he said.

Most common grade 3/4 treatment-emergent adverse events were higher with PVd than Vd, including neutropenia (42% vs 9%) and infections (31% vs 18%).

In conclusion, Dr Richardson said, “These results support the use of PVd in first relapse in patients with relapsed/refractory multiple myeloma and prior exposure to lenalidomide.”

Future analyses of the data will include correlatives, minimal residual disease, and quality of life, he said.

The trial was sponsored by Celgene. 

©ASCO/Michael R. Schmidt

CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.

“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.

Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.

Twice-weekly carfilzomib at 27 mg/m² is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.

To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.

At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.

Study design

The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.

Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.

The once-weekly group received carfilzomib 20 mg/m² intravenously on day 1 of cycle 1 and 70 mg/m² on days 1, 8, and 15 of all subsequent cycles.

The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m² on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).

The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.

Results

The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.

In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.

Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).

Safety

The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.

Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.

Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.

The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.

“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.

The ARROW study was supported by Amgen Inc.

©ASCO/Michael R. Schmidt

CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.

“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.

Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.

Twice-weekly carfilzomib at 27 mg/m² is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.

To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.

At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.

Study design

The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.

Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.

The once-weekly group received carfilzomib 20 mg/m² intravenously on day 1 of cycle 1 and 70 mg/m² on days 1, 8, and 15 of all subsequent cycles.

The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m² on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).

The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.

Results

The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.

In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.

Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).

Safety

The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.

Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.

Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.

The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.

“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.

The ARROW study was supported by Amgen Inc.

©ASCO/Michael R. Schmidt

CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.

“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.

Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.

Twice-weekly carfilzomib at 27 mg/m² is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.

To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.

At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.

Study design

The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.

Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.

The once-weekly group received carfilzomib 20 mg/m² intravenously on day 1 of cycle 1 and 70 mg/m² on days 1, 8, and 15 of all subsequent cycles.

The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m² on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).

The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.

Results

The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.

In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.

Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).

Safety

The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.

Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.

Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.

The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.

“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.

The ARROW study was supported by Amgen Inc.