Multiple Myeloma

Photo by Petr Kratochvil

CHICAGO—Researchers have identified a link between habitual physical activity (PA) and mortality among cancer patients.

Engaging in regular PA, both pre- and post-diagnosis, was associated with a significantly lower risk of death for the entire population studied and for patients with 8 specific types of cancer.

However, the association was not significant for patients with other cancer types, including hematologic malignancies.

Rikki Cannioto, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and her colleagues presented these findings at the AACR Annual Meeting 2018 (abstract 5254*).

The researchers examined the association between habitual PA and outcomes in 5807 cancer patients enrolled in the Data Bank and BioRepository at Roswell Park between 2003 and 2016.

The population was 54.8% female and 93% white. The average age at diagnosis was 60.6 years.

The researchers looked at patterns of PA over time, from the decade before the cancer was diagnosed and continuing for up to 1 year after diagnosis.

Patients who engaged in regular, moderate- to vigorous-intensity PA (such as walking, running, aerobics, or other cardiovascular exercise) both before and after their diagnosis were considered habitually active, whereas those who did not exercise regularly were considered habitually inactive.

Overall, 52% of patients reported habitual activity, and 19% reported habitual inactivity. Twenty-three percent of patients said their activity level decreased after diagnosis, and 6% said their activity level increased.

Patients were followed through January 31, 2018. The median time to follow-up was 53 months, and 33.7% of patients (n=1956) died during the follow-up period.

Results

The researchers found that patients who were active before and after diagnosis were 40% more likely to survive than those who were habitually inactive (P<0.001). Habitually inactive patients had a 66% increased risk of mortality compared to active patients.

The habitually active patients had a 37-month mean survival advantage over the inactive patients.

In addition, patients whose activity level increased after diagnosis had a 25% lower risk of death than patients who remained inactive after diagnosis.

The researchers observed a significant (P<0.05) association between habitual PA and decreased mortality in patients with breast, colon, prostate, bladder, endometrial, ovarian, esophageal, and skin cancers.

However, the association between PA and mortality was not significant for patients with hematologic malignancies (P=0.59) or kidney, liver, lung, pancreas, stomach, or “other” cancers.

The researchers said the associations between habitual PA and decreased mortality remained consistent regardless of a patient’s sex, tumor stage, smoking status, or body mass index.

“[W]hen it comes to exercise, something is better than nothing, but regular, weekly exercise seems to really make a difference,” Dr Cannioto said.

“In fact, patients who were physically active 3 or 4 days a week experienced an even greater benefit than those who exercised daily, and patients who had only 1 or 2 days of regular activity per week did nearly as well. This is particularly encouraging, as cancer patients and survivors can be overwhelmed by current physical activity recommendations.”

*Information in the abstract differs from the presentation.

Photo by Petr Kratochvil

CHICAGO—Researchers have identified a link between habitual physical activity (PA) and mortality among cancer patients.

Engaging in regular PA, both pre- and post-diagnosis, was associated with a significantly lower risk of death for the entire population studied and for patients with 8 specific types of cancer.

However, the association was not significant for patients with other cancer types, including hematologic malignancies.

Rikki Cannioto, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and her colleagues presented these findings at the AACR Annual Meeting 2018 (abstract 5254*).

The researchers examined the association between habitual PA and outcomes in 5807 cancer patients enrolled in the Data Bank and BioRepository at Roswell Park between 2003 and 2016.

The population was 54.8% female and 93% white. The average age at diagnosis was 60.6 years.

The researchers looked at patterns of PA over time, from the decade before the cancer was diagnosed and continuing for up to 1 year after diagnosis.

Patients who engaged in regular, moderate- to vigorous-intensity PA (such as walking, running, aerobics, or other cardiovascular exercise) both before and after their diagnosis were considered habitually active, whereas those who did not exercise regularly were considered habitually inactive.

Overall, 52% of patients reported habitual activity, and 19% reported habitual inactivity. Twenty-three percent of patients said their activity level decreased after diagnosis, and 6% said their activity level increased.

Patients were followed through January 31, 2018. The median time to follow-up was 53 months, and 33.7% of patients (n=1956) died during the follow-up period.

Results

The researchers found that patients who were active before and after diagnosis were 40% more likely to survive than those who were habitually inactive (P<0.001). Habitually inactive patients had a 66% increased risk of mortality compared to active patients.

The habitually active patients had a 37-month mean survival advantage over the inactive patients.

In addition, patients whose activity level increased after diagnosis had a 25% lower risk of death than patients who remained inactive after diagnosis.

The researchers observed a significant (P<0.05) association between habitual PA and decreased mortality in patients with breast, colon, prostate, bladder, endometrial, ovarian, esophageal, and skin cancers.

However, the association between PA and mortality was not significant for patients with hematologic malignancies (P=0.59) or kidney, liver, lung, pancreas, stomach, or “other” cancers.

The researchers said the associations between habitual PA and decreased mortality remained consistent regardless of a patient’s sex, tumor stage, smoking status, or body mass index.

“[W]hen it comes to exercise, something is better than nothing, but regular, weekly exercise seems to really make a difference,” Dr Cannioto said.

“In fact, patients who were physically active 3 or 4 days a week experienced an even greater benefit than those who exercised daily, and patients who had only 1 or 2 days of regular activity per week did nearly as well. This is particularly encouraging, as cancer patients and survivors can be overwhelmed by current physical activity recommendations.”

*Information in the abstract differs from the presentation.

Photo by Petr Kratochvil

CHICAGO—Researchers have identified a link between habitual physical activity (PA) and mortality among cancer patients.

Engaging in regular PA, both pre- and post-diagnosis, was associated with a significantly lower risk of death for the entire population studied and for patients with 8 specific types of cancer.

However, the association was not significant for patients with other cancer types, including hematologic malignancies.

Rikki Cannioto, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and her colleagues presented these findings at the AACR Annual Meeting 2018 (abstract 5254*).

The researchers examined the association between habitual PA and outcomes in 5807 cancer patients enrolled in the Data Bank and BioRepository at Roswell Park between 2003 and 2016.

The population was 54.8% female and 93% white. The average age at diagnosis was 60.6 years.

The researchers looked at patterns of PA over time, from the decade before the cancer was diagnosed and continuing for up to 1 year after diagnosis.

Patients who engaged in regular, moderate- to vigorous-intensity PA (such as walking, running, aerobics, or other cardiovascular exercise) both before and after their diagnosis were considered habitually active, whereas those who did not exercise regularly were considered habitually inactive.

Overall, 52% of patients reported habitual activity, and 19% reported habitual inactivity. Twenty-three percent of patients said their activity level decreased after diagnosis, and 6% said their activity level increased.

Patients were followed through January 31, 2018. The median time to follow-up was 53 months, and 33.7% of patients (n=1956) died during the follow-up period.

Results

The researchers found that patients who were active before and after diagnosis were 40% more likely to survive than those who were habitually inactive (P<0.001). Habitually inactive patients had a 66% increased risk of mortality compared to active patients.

The habitually active patients had a 37-month mean survival advantage over the inactive patients.

In addition, patients whose activity level increased after diagnosis had a 25% lower risk of death than patients who remained inactive after diagnosis.

The researchers observed a significant (P<0.05) association between habitual PA and decreased mortality in patients with breast, colon, prostate, bladder, endometrial, ovarian, esophageal, and skin cancers.

However, the association between PA and mortality was not significant for patients with hematologic malignancies (P=0.59) or kidney, liver, lung, pancreas, stomach, or “other” cancers.

The researchers said the associations between habitual PA and decreased mortality remained consistent regardless of a patient’s sex, tumor stage, smoking status, or body mass index.

“[W]hen it comes to exercise, something is better than nothing, but regular, weekly exercise seems to really make a difference,” Dr Cannioto said.

“In fact, patients who were physically active 3 or 4 days a week experienced an even greater benefit than those who exercised daily, and patients who had only 1 or 2 days of regular activity per week did nearly as well. This is particularly encouraging, as cancer patients and survivors can be overwhelmed by current physical activity recommendations.”

*Information in the abstract differs from the presentation.

Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

multiple myeloma

CHICAGO—Early phase 1 results suggest a chimeric antigen receptor (CAR) T-cell therapy can induce tumor regression in heavily pretreated patients with multiple myeloma (MM).

The therapy, P-BCMA-101, has only been tested in 3 patients in the lowest dose cohort.

However, signs of efficacy have been seen in all 3 patients, including a lasting partial response in 1 patient.

There have been no dose-limiting toxicities, and none of the patients have developed cytokine release syndrome (CRS).

“The results from the first cohort of the phase 1 P-BCMA-101 study have surpassed historical benchmarks of safety and efficacy in multiple myeloma at this dose level and give us confidence to move ahead into additional dose cohorts,” said Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, Inc.

Dr Ostertag and his colleagues presented these results at the AACR Annual Meeting 2018 (abstract CT130). The trial is sponsored by Poseida Therapeutics, Inc.

The trial is enrolling patients with relapsed/refractory MM who have received a proteasome inhibitor and immunomodulatory agent.

Conditioning consists of standard cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) on days -5 to -3. Patients then receive a single dose of P-BCMA-101 on day 0.

The trial has a 3+3 dose-escalation design, with up to 6 dose levels. The first dose level is 0.75 x 10⁶ P-BCMA-101 cells/kg.

The 3 patients who have received this dose had 6 to 9 prior therapies.

Patient 1

The first patient was a 54-year-old female with lambda light chain MM. She had t(11;14), del13q14, and 11q23(x3).

Before she received P-BCMA-101, the patient had an increase in free light chains (FLCs) to 3290 mg/L, which caused renal failure. She was treated with cyclophosphamide/prednisone and plasmapheresis bridging therapy before proceeding to P-BCMA-101.

The patient achieved a partial response 2 weeks after receiving P-BCMA-101, and this has persisted through week 12.  She had a maximal reduction in urine M-protein of 92% and a reduction in plasma FLCs of 79%.

The patient did not experience any adverse events (AEs) considered related to P-BCMA-101.

Patient 2

The second patient was a 50-year-old female with oligosecretory kappa light chain MM and plasmacytomas. She had del17p (TP53) and 11q13(x3).

Due to enlarging plasmacytomas, the patient was treated with DT-PACE (dexamethasone plus thalidomide with cisplatin, doxorubicin, cyclophosphamide, and etoposide) before receiving P-BCMA-101.

Her bone plasmacytomas resolved to below background within 4 to 8 weeks of P-BCMA-101 administration, but 1 new non-bone lesion appeared months later.

AEs considered at least possibly related to treatment in this patient included grade 2-4 neutropenia as well as grade 3-4 thrombocytopenia.

Patient 3

The third patient was a 65-year-old female with lambda light chain MM and del13q14.

Her urine M-protein and FLCs briefly dipped and rose after she received bridging therapy with lenalidomide and dexamethasone, but they decreased at 4 weeks after P-BCMA-101 administration, which corresponded with P-BCMA-101 expansion in the peripheral blood.

AEs considered at least possibly related to treatment included easy bruising (grade 1), fatigue (grade 2), febrile neutropenia (grade 3), hypogammaglobinemia (grade 2), neutropenia (grade 2-3), and thrombocytopenia (grade 3-4).

“The lack of cytokine release syndrome in any of the 3 patients, in spite of marked efficacy, is unprecedented at this dose, which we believe is attributable to multiple differentiated aspects of our technology, resulting in a highly purified CAR T product with a high percentage of cells with a T stem cell memory phenotype,” Dr Ostertag said.

In addition to a lack of CRS, there were no dose-limiting toxicities. Therefore, the dose has been escalated to 2 x 10⁶ P-BCMA-101+ CAR T cells/kg for the next patient cohort. The first patient has been treated at this dose level, with no CRS yet reported.

 

About P-BCMA-101

P-BCMA-101 employs a B-cell maturation antigen-specific Centyrin™ fused to a second-generation CAR scaffold (a CARTyrin) rather than a single-chain variable fragment (scFv).

Centyrins have similar binding affinities as scFvs but are said to be potentially less immunogenic than scFvs, more stable at the cell surface, and resistant to antigen/ligand-independent tonic signaling.

P-BCMA-101 is engineered using PiggyBac™, a transposon-based system requiring only mRNA and plasmid DNA (no virus).

The increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be activated to enable depletion in case AEs occur. And the selectable gene allows for enrichment of CAR+ cells.

multiple myeloma

CHICAGO—Early phase 1 results suggest a chimeric antigen receptor (CAR) T-cell therapy can induce tumor regression in heavily pretreated patients with multiple myeloma (MM).

The therapy, P-BCMA-101, has only been tested in 3 patients in the lowest dose cohort.

However, signs of efficacy have been seen in all 3 patients, including a lasting partial response in 1 patient.

There have been no dose-limiting toxicities, and none of the patients have developed cytokine release syndrome (CRS).

“The results from the first cohort of the phase 1 P-BCMA-101 study have surpassed historical benchmarks of safety and efficacy in multiple myeloma at this dose level and give us confidence to move ahead into additional dose cohorts,” said Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, Inc.

Dr Ostertag and his colleagues presented these results at the AACR Annual Meeting 2018 (abstract CT130). The trial is sponsored by Poseida Therapeutics, Inc.

The trial is enrolling patients with relapsed/refractory MM who have received a proteasome inhibitor and immunomodulatory agent.

Conditioning consists of standard cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) on days -5 to -3. Patients then receive a single dose of P-BCMA-101 on day 0.

The trial has a 3+3 dose-escalation design, with up to 6 dose levels. The first dose level is 0.75 x 10⁶ P-BCMA-101 cells/kg.

The 3 patients who have received this dose had 6 to 9 prior therapies.

Patient 1

The first patient was a 54-year-old female with lambda light chain MM. She had t(11;14), del13q14, and 11q23(x3).

Before she received P-BCMA-101, the patient had an increase in free light chains (FLCs) to 3290 mg/L, which caused renal failure. She was treated with cyclophosphamide/prednisone and plasmapheresis bridging therapy before proceeding to P-BCMA-101.

The patient achieved a partial response 2 weeks after receiving P-BCMA-101, and this has persisted through week 12.  She had a maximal reduction in urine M-protein of 92% and a reduction in plasma FLCs of 79%.

The patient did not experience any adverse events (AEs) considered related to P-BCMA-101.

Patient 2

The second patient was a 50-year-old female with oligosecretory kappa light chain MM and plasmacytomas. She had del17p (TP53) and 11q13(x3).

Due to enlarging plasmacytomas, the patient was treated with DT-PACE (dexamethasone plus thalidomide with cisplatin, doxorubicin, cyclophosphamide, and etoposide) before receiving P-BCMA-101.

Her bone plasmacytomas resolved to below background within 4 to 8 weeks of P-BCMA-101 administration, but 1 new non-bone lesion appeared months later.

AEs considered at least possibly related to treatment in this patient included grade 2-4 neutropenia as well as grade 3-4 thrombocytopenia.

Patient 3

The third patient was a 65-year-old female with lambda light chain MM and del13q14.

Her urine M-protein and FLCs briefly dipped and rose after she received bridging therapy with lenalidomide and dexamethasone, but they decreased at 4 weeks after P-BCMA-101 administration, which corresponded with P-BCMA-101 expansion in the peripheral blood.

AEs considered at least possibly related to treatment included easy bruising (grade 1), fatigue (grade 2), febrile neutropenia (grade 3), hypogammaglobinemia (grade 2), neutropenia (grade 2-3), and thrombocytopenia (grade 3-4).

“The lack of cytokine release syndrome in any of the 3 patients, in spite of marked efficacy, is unprecedented at this dose, which we believe is attributable to multiple differentiated aspects of our technology, resulting in a highly purified CAR T product with a high percentage of cells with a T stem cell memory phenotype,” Dr Ostertag said.

In addition to a lack of CRS, there were no dose-limiting toxicities. Therefore, the dose has been escalated to 2 x 10⁶ P-BCMA-101+ CAR T cells/kg for the next patient cohort. The first patient has been treated at this dose level, with no CRS yet reported.

 

About P-BCMA-101

P-BCMA-101 employs a B-cell maturation antigen-specific Centyrin™ fused to a second-generation CAR scaffold (a CARTyrin) rather than a single-chain variable fragment (scFv).

Centyrins have similar binding affinities as scFvs but are said to be potentially less immunogenic than scFvs, more stable at the cell surface, and resistant to antigen/ligand-independent tonic signaling.

P-BCMA-101 is engineered using PiggyBac™, a transposon-based system requiring only mRNA and plasmid DNA (no virus).

The increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be activated to enable depletion in case AEs occur. And the selectable gene allows for enrichment of CAR+ cells.

multiple myeloma

CHICAGO—Early phase 1 results suggest a chimeric antigen receptor (CAR) T-cell therapy can induce tumor regression in heavily pretreated patients with multiple myeloma (MM).

The therapy, P-BCMA-101, has only been tested in 3 patients in the lowest dose cohort.

However, signs of efficacy have been seen in all 3 patients, including a lasting partial response in 1 patient.

There have been no dose-limiting toxicities, and none of the patients have developed cytokine release syndrome (CRS).

“The results from the first cohort of the phase 1 P-BCMA-101 study have surpassed historical benchmarks of safety and efficacy in multiple myeloma at this dose level and give us confidence to move ahead into additional dose cohorts,” said Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, Inc.

Dr Ostertag and his colleagues presented these results at the AACR Annual Meeting 2018 (abstract CT130). The trial is sponsored by Poseida Therapeutics, Inc.

The trial is enrolling patients with relapsed/refractory MM who have received a proteasome inhibitor and immunomodulatory agent.

Conditioning consists of standard cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) on days -5 to -3. Patients then receive a single dose of P-BCMA-101 on day 0.

The trial has a 3+3 dose-escalation design, with up to 6 dose levels. The first dose level is 0.75 x 10⁶ P-BCMA-101 cells/kg.

The 3 patients who have received this dose had 6 to 9 prior therapies.

Patient 1

The first patient was a 54-year-old female with lambda light chain MM. She had t(11;14), del13q14, and 11q23(x3).

Before she received P-BCMA-101, the patient had an increase in free light chains (FLCs) to 3290 mg/L, which caused renal failure. She was treated with cyclophosphamide/prednisone and plasmapheresis bridging therapy before proceeding to P-BCMA-101.

The patient achieved a partial response 2 weeks after receiving P-BCMA-101, and this has persisted through week 12.  She had a maximal reduction in urine M-protein of 92% and a reduction in plasma FLCs of 79%.

The patient did not experience any adverse events (AEs) considered related to P-BCMA-101.

Patient 2

The second patient was a 50-year-old female with oligosecretory kappa light chain MM and plasmacytomas. She had del17p (TP53) and 11q13(x3).

Due to enlarging plasmacytomas, the patient was treated with DT-PACE (dexamethasone plus thalidomide with cisplatin, doxorubicin, cyclophosphamide, and etoposide) before receiving P-BCMA-101.

Her bone plasmacytomas resolved to below background within 4 to 8 weeks of P-BCMA-101 administration, but 1 new non-bone lesion appeared months later.

AEs considered at least possibly related to treatment in this patient included grade 2-4 neutropenia as well as grade 3-4 thrombocytopenia.

Patient 3

The third patient was a 65-year-old female with lambda light chain MM and del13q14.

Her urine M-protein and FLCs briefly dipped and rose after she received bridging therapy with lenalidomide and dexamethasone, but they decreased at 4 weeks after P-BCMA-101 administration, which corresponded with P-BCMA-101 expansion in the peripheral blood.

AEs considered at least possibly related to treatment included easy bruising (grade 1), fatigue (grade 2), febrile neutropenia (grade 3), hypogammaglobinemia (grade 2), neutropenia (grade 2-3), and thrombocytopenia (grade 3-4).

“The lack of cytokine release syndrome in any of the 3 patients, in spite of marked efficacy, is unprecedented at this dose, which we believe is attributable to multiple differentiated aspects of our technology, resulting in a highly purified CAR T product with a high percentage of cells with a T stem cell memory phenotype,” Dr Ostertag said.

In addition to a lack of CRS, there were no dose-limiting toxicities. Therefore, the dose has been escalated to 2 x 10⁶ P-BCMA-101+ CAR T cells/kg for the next patient cohort. The first patient has been treated at this dose level, with no CRS yet reported.

 

About P-BCMA-101

P-BCMA-101 employs a B-cell maturation antigen-specific Centyrin™ fused to a second-generation CAR scaffold (a CARTyrin) rather than a single-chain variable fragment (scFv).

Centyrins have similar binding affinities as scFvs but are said to be potentially less immunogenic than scFvs, more stable at the cell surface, and resistant to antigen/ligand-independent tonic signaling.

P-BCMA-101 is engineered using PiggyBac™, a transposon-based system requiring only mRNA and plasmid DNA (no virus).

The increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be activated to enable depletion in case AEs occur. And the selectable gene allows for enrichment of CAR+ cells.

Photo by Aaron Logan

CHICAGO—A BET inhibitor can have potent and long-lasting effects against leukemia and multiple myeloma (MM), according to researchers.

The inhibitor, TG-1601 (or CK-103), exhibited cytotoxicity in MM and leukemia cell lines but did not affect the growth of normal cell lines.

TG-1601 also reduced tumor volume in mouse models of MM and acute myeloid leukemia (AML), and drug holidays had little impact on this activity.

Furthermore, researchers observed enduring MYC inhibition in mice treated with TG-1601.

This research was presented at the AACR Annual Meeting 2018 (abstract 5790).

The work was conducted by researchers from TG Therapeutics and Checkpoint Therapeutics—the companies developing TG-1601—as well as Jubilant Biosys.

In vitro activity

Researchers assessed the cytotoxic activity of TG-1601 in leukemia, MM, and normal cell lines by incubating the cells with increasing concentrations of the drug for 72 hours.

The results suggested TG-1601 inhibits MM and leukemia cell growth, as all EC₅₀ values were below 100 nM.

In the leukemia cell lines, EC₅₀ values were 35 nM (Jurkat), 31 nM (HEL92.1.7), 24 nM (CCRF-CEM and MV4-11), and 18 nM (OCI-AML3).

In the MM cell lines, EC₅₀ values were 85 nM (RPMI8226), 32 nM (KMS28PE), 24 nM (KMS28BM), 21 nM (MOLP8), and 15 nM (MM1s).

In the normal cell lines (Beas2B and WT9-12), cell growth wasn’t inhibited more than 50% with TG-1601 at 10 μM.

In vivo activity

For their MM model, researchers used mice inoculated with MM1 cells. The mice received TG-1601 at 10 mg/kg twice a day.

At day 17 after treatment initiation, there was a 70% reduction in tumor volume. During a week-long drug holiday, tumors did not grow back as fast in TG-1601-treated mice as they did in vehicle control mice.

For their AML model, researchers used mice inoculated with MV4-11 cells. The mice received TG-1601 as a single dose of 20 mg/kg/day—continuously or with 2, 3, or 4 days off per week—or at 10 mg/kg twice a day.

At day 15, 100% of mice that received the drug at 10 mg/kg twice a day were tumor-free. Mice that received the single 20 mg/kg dose had a 94% reduction in tumor volume.

The reduction in tumor volume was 91% in mice with the 2-day drug holiday, 78% in those with the 3-day holiday, and 82% in those with the 4-day holiday.

The researchers also found that TG-1601 had synergistic antitumor activity with an anti-PD-1 antibody in a mouse model of melanoma.

Pharmacodynamic activity

In the MV4-11 cell line, TG-1601 induced “rapid” downregulation of MYC and BCL2 and an increase of p21 mRNA, according to the researchers.

The team also assessed MYC expression in mice with MV4-11 tumors. They said MYC levels rapidly decreased in the tumors and were undetectable at 3 hours after a single dose of TG-1601.

The researchers noted that, at 24 hours after dosing, TG-1601 was cleared from the tumor. However, MYC levels remained below 40% their initial level.

The team said this suggests a long-lasting effect of TG-1601 that may be attributed to its enhanced binding affinity.

“These data demonstrate [TG-1601’s] potential to be a novel BET inhibitor that potently inhibits MYC expression,” said James F. Oliviero, president and chief executive officer of Checkpoint Therapeutics.

“We believe the preclinical data presented today provides encouraging evidence to support the development of [TG-1601] as an anticancer agent, alone and in combination with our anti-PD-L1 antibody, and look forward to the advancement of [TG-1601] into a first-in-human phase 1 trial expected to commence later this year.”

Photo by Aaron Logan

CHICAGO—A BET inhibitor can have potent and long-lasting effects against leukemia and multiple myeloma (MM), according to researchers.

The inhibitor, TG-1601 (or CK-103), exhibited cytotoxicity in MM and leukemia cell lines but did not affect the growth of normal cell lines.

TG-1601 also reduced tumor volume in mouse models of MM and acute myeloid leukemia (AML), and drug holidays had little impact on this activity.

Furthermore, researchers observed enduring MYC inhibition in mice treated with TG-1601.

This research was presented at the AACR Annual Meeting 2018 (abstract 5790).

The work was conducted by researchers from TG Therapeutics and Checkpoint Therapeutics—the companies developing TG-1601—as well as Jubilant Biosys.

In vitro activity

Researchers assessed the cytotoxic activity of TG-1601 in leukemia, MM, and normal cell lines by incubating the cells with increasing concentrations of the drug for 72 hours.

The results suggested TG-1601 inhibits MM and leukemia cell growth, as all EC₅₀ values were below 100 nM.

In the leukemia cell lines, EC₅₀ values were 35 nM (Jurkat), 31 nM (HEL92.1.7), 24 nM (CCRF-CEM and MV4-11), and 18 nM (OCI-AML3).

In the MM cell lines, EC₅₀ values were 85 nM (RPMI8226), 32 nM (KMS28PE), 24 nM (KMS28BM), 21 nM (MOLP8), and 15 nM (MM1s).

In the normal cell lines (Beas2B and WT9-12), cell growth wasn’t inhibited more than 50% with TG-1601 at 10 μM.

In vivo activity

For their MM model, researchers used mice inoculated with MM1 cells. The mice received TG-1601 at 10 mg/kg twice a day.

At day 17 after treatment initiation, there was a 70% reduction in tumor volume. During a week-long drug holiday, tumors did not grow back as fast in TG-1601-treated mice as they did in vehicle control mice.

For their AML model, researchers used mice inoculated with MV4-11 cells. The mice received TG-1601 as a single dose of 20 mg/kg/day—continuously or with 2, 3, or 4 days off per week—or at 10 mg/kg twice a day.

At day 15, 100% of mice that received the drug at 10 mg/kg twice a day were tumor-free. Mice that received the single 20 mg/kg dose had a 94% reduction in tumor volume.

The reduction in tumor volume was 91% in mice with the 2-day drug holiday, 78% in those with the 3-day holiday, and 82% in those with the 4-day holiday.

The researchers also found that TG-1601 had synergistic antitumor activity with an anti-PD-1 antibody in a mouse model of melanoma.

Pharmacodynamic activity

In the MV4-11 cell line, TG-1601 induced “rapid” downregulation of MYC and BCL2 and an increase of p21 mRNA, according to the researchers.

The team also assessed MYC expression in mice with MV4-11 tumors. They said MYC levels rapidly decreased in the tumors and were undetectable at 3 hours after a single dose of TG-1601.

The researchers noted that, at 24 hours after dosing, TG-1601 was cleared from the tumor. However, MYC levels remained below 40% their initial level.

The team said this suggests a long-lasting effect of TG-1601 that may be attributed to its enhanced binding affinity.

“These data demonstrate [TG-1601’s] potential to be a novel BET inhibitor that potently inhibits MYC expression,” said James F. Oliviero, president and chief executive officer of Checkpoint Therapeutics.

“We believe the preclinical data presented today provides encouraging evidence to support the development of [TG-1601] as an anticancer agent, alone and in combination with our anti-PD-L1 antibody, and look forward to the advancement of [TG-1601] into a first-in-human phase 1 trial expected to commence later this year.”

Photo by Aaron Logan

CHICAGO—A BET inhibitor can have potent and long-lasting effects against leukemia and multiple myeloma (MM), according to researchers.

The inhibitor, TG-1601 (or CK-103), exhibited cytotoxicity in MM and leukemia cell lines but did not affect the growth of normal cell lines.

TG-1601 also reduced tumor volume in mouse models of MM and acute myeloid leukemia (AML), and drug holidays had little impact on this activity.

Furthermore, researchers observed enduring MYC inhibition in mice treated with TG-1601.

This research was presented at the AACR Annual Meeting 2018 (abstract 5790).

The work was conducted by researchers from TG Therapeutics and Checkpoint Therapeutics—the companies developing TG-1601—as well as Jubilant Biosys.

In vitro activity

Researchers assessed the cytotoxic activity of TG-1601 in leukemia, MM, and normal cell lines by incubating the cells with increasing concentrations of the drug for 72 hours.

The results suggested TG-1601 inhibits MM and leukemia cell growth, as all EC₅₀ values were below 100 nM.

In the leukemia cell lines, EC₅₀ values were 35 nM (Jurkat), 31 nM (HEL92.1.7), 24 nM (CCRF-CEM and MV4-11), and 18 nM (OCI-AML3).

In the MM cell lines, EC₅₀ values were 85 nM (RPMI8226), 32 nM (KMS28PE), 24 nM (KMS28BM), 21 nM (MOLP8), and 15 nM (MM1s).

In the normal cell lines (Beas2B and WT9-12), cell growth wasn’t inhibited more than 50% with TG-1601 at 10 μM.

In vivo activity

For their MM model, researchers used mice inoculated with MM1 cells. The mice received TG-1601 at 10 mg/kg twice a day.

At day 17 after treatment initiation, there was a 70% reduction in tumor volume. During a week-long drug holiday, tumors did not grow back as fast in TG-1601-treated mice as they did in vehicle control mice.

For their AML model, researchers used mice inoculated with MV4-11 cells. The mice received TG-1601 as a single dose of 20 mg/kg/day—continuously or with 2, 3, or 4 days off per week—or at 10 mg/kg twice a day.

At day 15, 100% of mice that received the drug at 10 mg/kg twice a day were tumor-free. Mice that received the single 20 mg/kg dose had a 94% reduction in tumor volume.

The reduction in tumor volume was 91% in mice with the 2-day drug holiday, 78% in those with the 3-day holiday, and 82% in those with the 4-day holiday.

The researchers also found that TG-1601 had synergistic antitumor activity with an anti-PD-1 antibody in a mouse model of melanoma.

Pharmacodynamic activity

In the MV4-11 cell line, TG-1601 induced “rapid” downregulation of MYC and BCL2 and an increase of p21 mRNA, according to the researchers.

The team also assessed MYC expression in mice with MV4-11 tumors. They said MYC levels rapidly decreased in the tumors and were undetectable at 3 hours after a single dose of TG-1601.

The researchers noted that, at 24 hours after dosing, TG-1601 was cleared from the tumor. However, MYC levels remained below 40% their initial level.

The team said this suggests a long-lasting effect of TG-1601 that may be attributed to its enhanced binding affinity.

“These data demonstrate [TG-1601’s] potential to be a novel BET inhibitor that potently inhibits MYC expression,” said James F. Oliviero, president and chief executive officer of Checkpoint Therapeutics.

“We believe the preclinical data presented today provides encouraging evidence to support the development of [TG-1601] as an anticancer agent, alone and in combination with our anti-PD-L1 antibody, and look forward to the advancement of [TG-1601] into a first-in-human phase 1 trial expected to commence later this year.”

 

In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.

Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.

Nephron/Wikimedia Commons

“This combination resulted in promising and durable responses,” Ajai Chari, MD, of the Tisch Cancer Institute at Mount Sinai Hospital, New York, and coauthors wrote.

The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.

Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.

In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.

To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.

 

A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.

Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.

Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.

Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.

Enrollment in phase 2b of the study is ongoing.

Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.

SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.

 

In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.

Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.

Nephron/Wikimedia Commons

“This combination resulted in promising and durable responses,” Ajai Chari, MD, of the Tisch Cancer Institute at Mount Sinai Hospital, New York, and coauthors wrote.

The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.

Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.

In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.

To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.

 

A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.

Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.

Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.

Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.

Enrollment in phase 2b of the study is ongoing.

Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.

SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.

 

In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.

Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.

Nephron/Wikimedia Commons

“This combination resulted in promising and durable responses,” Ajai Chari, MD, of the Tisch Cancer Institute at Mount Sinai Hospital, New York, and coauthors wrote.

The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.

Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.

In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.

To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.

 

A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.

Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.

Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.

Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.

Enrollment in phase 2b of the study is ongoing.

Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.

SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.

Photo from Business Wire

Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran^®, is now available in the US.

Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.

Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.

Photo from Business Wire

Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran^®, is now available in the US.

Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.

Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.

Photo from Business Wire

Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran^®, is now available in the US.

Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.

Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).

The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.

In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.

“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

About selinexor

Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.

Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.

Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.

In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.

Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.

multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).

The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.

In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.

“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

About selinexor

Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.

Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.

Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.

In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.

Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.

multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).

The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.

In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.

“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

About selinexor

Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.

Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.

Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.

In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.

Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.