Multiple Myeloma

Treatment with selinexor and low-dose dexamethasone can provide a “meaningful clinical benefit” in patients with penta-refractory multiple myeloma, according to the principal investigator of the STORM trial.

Nephron/Wikimedia Commons

Updated results from this phase 2 trial showed that selinexor and low-dose dexamethasone produced an overall response rate of 26.2% and a clinical benefit rate of 39.3%. The median progression-free survival was 3.7 months and the median overall survival was 8.6 months.

The trial’s principal investigator, Sundar Jagannath, MBBS, of the Icahn School of Medicine at Mount Sinai, New York, presented these results at the annual meeting of the Society of Hematologic Oncology.

“The additional phase 2b clinical results… are very encouraging for the patients suffering from penta-refractory multiple myeloma and their families,” Dr. Jagannath said in a statement. “Of particular significance, for the nearly 40% of patients who had a minimal response or better, the median survival was 15.6 months, which provided the opportunity for a meaningful clinical benefit for patients on the STORM [Selinexor Treatment of Refractory Myeloma] study.”

STORM (NCT02336815) included 122 patients with penta-refractory multiple myeloma. They had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, alkylating agents, and glucocorticoids. Their disease was refractory to glucocorticoids, at least one proteasome inhibitor, at least one immunomodulatory drug, daratumumab, and their most recent therapy.

The patients had received a median of seven prior treatment regimens. Their median age was 65 years, a little more than half were men, and more than half had high-risk cytogenetics. Patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.Two patients (1.6%) achieved stringent complete responses. They also had minimal residual disease negativity, one at the level of 1 x 10^–6 and one at 1 x 10^–4.

Very good partial responses were seen in 4.9% of patients, 19.7% had partial responses, 13.1% had minimal responses (MRs), and 39.3% had stable disease. Progressive disease occurred in 13.1% of patients; 8.2% were not evaluable for response.

[email protected]

SOURCE: Jagannath S et al. SOHO 2018, Abstract MM-255

Treatment with selinexor and low-dose dexamethasone can provide a “meaningful clinical benefit” in patients with penta-refractory multiple myeloma, according to the principal investigator of the STORM trial.

Nephron/Wikimedia Commons

Updated results from this phase 2 trial showed that selinexor and low-dose dexamethasone produced an overall response rate of 26.2% and a clinical benefit rate of 39.3%. The median progression-free survival was 3.7 months and the median overall survival was 8.6 months.

The trial’s principal investigator, Sundar Jagannath, MBBS, of the Icahn School of Medicine at Mount Sinai, New York, presented these results at the annual meeting of the Society of Hematologic Oncology.

“The additional phase 2b clinical results… are very encouraging for the patients suffering from penta-refractory multiple myeloma and their families,” Dr. Jagannath said in a statement. “Of particular significance, for the nearly 40% of patients who had a minimal response or better, the median survival was 15.6 months, which provided the opportunity for a meaningful clinical benefit for patients on the STORM [Selinexor Treatment of Refractory Myeloma] study.”

STORM (NCT02336815) included 122 patients with penta-refractory multiple myeloma. They had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, alkylating agents, and glucocorticoids. Their disease was refractory to glucocorticoids, at least one proteasome inhibitor, at least one immunomodulatory drug, daratumumab, and their most recent therapy.

The patients had received a median of seven prior treatment regimens. Their median age was 65 years, a little more than half were men, and more than half had high-risk cytogenetics. Patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.Two patients (1.6%) achieved stringent complete responses. They also had minimal residual disease negativity, one at the level of 1 x 10^–6 and one at 1 x 10^–4.

Very good partial responses were seen in 4.9% of patients, 19.7% had partial responses, 13.1% had minimal responses (MRs), and 39.3% had stable disease. Progressive disease occurred in 13.1% of patients; 8.2% were not evaluable for response.

[email protected]

SOURCE: Jagannath S et al. SOHO 2018, Abstract MM-255

Treatment with selinexor and low-dose dexamethasone can provide a “meaningful clinical benefit” in patients with penta-refractory multiple myeloma, according to the principal investigator of the STORM trial.

Nephron/Wikimedia Commons

Updated results from this phase 2 trial showed that selinexor and low-dose dexamethasone produced an overall response rate of 26.2% and a clinical benefit rate of 39.3%. The median progression-free survival was 3.7 months and the median overall survival was 8.6 months.

The trial’s principal investigator, Sundar Jagannath, MBBS, of the Icahn School of Medicine at Mount Sinai, New York, presented these results at the annual meeting of the Society of Hematologic Oncology.

“The additional phase 2b clinical results… are very encouraging for the patients suffering from penta-refractory multiple myeloma and their families,” Dr. Jagannath said in a statement. “Of particular significance, for the nearly 40% of patients who had a minimal response or better, the median survival was 15.6 months, which provided the opportunity for a meaningful clinical benefit for patients on the STORM [Selinexor Treatment of Refractory Myeloma] study.”

STORM (NCT02336815) included 122 patients with penta-refractory multiple myeloma. They had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, alkylating agents, and glucocorticoids. Their disease was refractory to glucocorticoids, at least one proteasome inhibitor, at least one immunomodulatory drug, daratumumab, and their most recent therapy.

The patients had received a median of seven prior treatment regimens. Their median age was 65 years, a little more than half were men, and more than half had high-risk cytogenetics. Patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.Two patients (1.6%) achieved stringent complete responses. They also had minimal residual disease negativity, one at the level of 1 x 10^–6 and one at 1 x 10^–4.

Very good partial responses were seen in 4.9% of patients, 19.7% had partial responses, 13.1% had minimal responses (MRs), and 39.3% had stable disease. Progressive disease occurred in 13.1% of patients; 8.2% were not evaluable for response.

[email protected]

SOURCE: Jagannath S et al. SOHO 2018, Abstract MM-255

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

multiple myeloma

BOSTON—Early results from a phase 1 trial suggest the chimeric antigen receptor (CAR) T-cell therapy P-BCMA-101 can produce responses in patients with relapsed/refractory multiple myeloma (MM).

All 11 patients treated have experienced some clinical response, with 8 patients achieving a partial response (PR) or better.

The most common adverse events were neutropenia and thrombocytopenia. One patient was suspected to have cytokine release syndrome, but the condition resolved without use of tociluzimab or steroids.

These results were presented at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics Inc., the company developing P-BCMA-101.

Dr. Ostertag presented data on 11 patients with heavily pretreated MM. They had a median of six prior therapies. Their median age was 60, and 73% were considered high risk.

Prior to receiving P-BCMA-101, patients received conditioning with fludarabine (30 mg/m²) and cyclophosphamide (300 mg/m²) for 3 days.

Patients were then treated across three dose groups with average CAR T-cell doses of 51×10⁶ (n=3), 152×10⁶ (n=7), and 430×10⁶ (n=1).

As of August 10, 2018, all 11 patients were still on study.

There were no dose-limiting toxicities. Eight patients developed neutropenia, and 5 had thrombocytopenia.

Researchers suspected cytokine release syndrome in one patient, but the condition resolved without tociluzimab or steroid treatment. There was no neurotoxicity reported, and none of the patients required admission to an intensive care unit.

All patients showed improvement in biomarkers following treatment.

Ten patients were evaluable for response by International Myeloma Working Group criteria. Seven of these patients achieved at least a PR, including very good partial responses (VGPRs) and stringent complete response (CR).

The eleventh patient also responded to treatment, but this patient has oligosecretory disease and was only evaluable by PET. The patient had a near-CR by PET.

Poseida Therapeutics would not disclose additional details regarding how many patients achieved a PR, VGPR, or CR, but the company plans to release more information on response at an upcoming meeting.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assessments,” Dr. Ostertag said.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

This study (NCT03288493) is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.

A novel inhibitor of AKT pathway signaling showed significant cytotoxic activity in mouse models and in human cells isolated from patients with primary or relapsed multiple myeloma (MM), investigators reported.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The experimental agent, labeled HS1793, is a derivative of the naturally occurring antioxidant compound resveratrol. In preclinical studies, HS1793 was shown to offer “great promise in eliminating MM cells and improving therapeutic responses in primary and relapsed/refractory MM patients,” according to Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues.

In a series of experiments, described in the journal Cancer Letters, the investigators demonstrated that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in multiple myeloma cells, and was cytotoxic and specific for myeloma cells in a mouse model of human metastatic myeloma, and in samples of human multiple myeloma cells.

When activated, AKT promotes oncogenesis by in turn activating other downstream pathways involved in proliferation or survival of malignant cells.

“AKT is frequently activated in MM cells and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They first screened 400 compounds, and narrowed in on resveratrol analogs, eventually choosing HS1793 as the most promising candidate.

This first experiment found evidence that suggested that the compound inhibits AKT activation by interfering with the interaction between AKT and its promoter HSP90.

They then showed in human MM cell lines that the antimyeloma action of HS1793 appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In a separate series of experiments, they found that the inhibition by HS1793 of AKT/HSP90 interaction results in cell death by suppressing nuclear factor kappa–B (NF-KB) pathway signaling. The investigators had previously reported that a different compound, an inhibitor of spindle protein kinesin, induced MM cell death via inhibition of NF-KB signaling.

Next, the investigators showed that HS1793-induced cell death was caused by the direct inhibition of AKT that in turn suppressed NF-KB activation.

Finally, they showed in a mouse model of multiple myeloma metastatic to bone that HS1793 “dramatically decreased” lytic skull and femur lesions in treated mice, compared with mice treated with a vehicle placebo, and increased survival of the mice that received the AKT inhibitor.

They also showed that HS1793 was cytotoxic to multiple myeloma cells but not to normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” they wrote.

The study was supported by grants from the Korean government. The researchers reported having no potential conflicts of interest.

SOURCE: Song IS et al. Cancer Lett. 2018;432:205-15.

A novel inhibitor of AKT pathway signaling showed significant cytotoxic activity in mouse models and in human cells isolated from patients with primary or relapsed multiple myeloma (MM), investigators reported.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The experimental agent, labeled HS1793, is a derivative of the naturally occurring antioxidant compound resveratrol. In preclinical studies, HS1793 was shown to offer “great promise in eliminating MM cells and improving therapeutic responses in primary and relapsed/refractory MM patients,” according to Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues.

In a series of experiments, described in the journal Cancer Letters, the investigators demonstrated that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in multiple myeloma cells, and was cytotoxic and specific for myeloma cells in a mouse model of human metastatic myeloma, and in samples of human multiple myeloma cells.

When activated, AKT promotes oncogenesis by in turn activating other downstream pathways involved in proliferation or survival of malignant cells.

“AKT is frequently activated in MM cells and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They first screened 400 compounds, and narrowed in on resveratrol analogs, eventually choosing HS1793 as the most promising candidate.

This first experiment found evidence that suggested that the compound inhibits AKT activation by interfering with the interaction between AKT and its promoter HSP90.

They then showed in human MM cell lines that the antimyeloma action of HS1793 appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In a separate series of experiments, they found that the inhibition by HS1793 of AKT/HSP90 interaction results in cell death by suppressing nuclear factor kappa–B (NF-KB) pathway signaling. The investigators had previously reported that a different compound, an inhibitor of spindle protein kinesin, induced MM cell death via inhibition of NF-KB signaling.

Next, the investigators showed that HS1793-induced cell death was caused by the direct inhibition of AKT that in turn suppressed NF-KB activation.

Finally, they showed in a mouse model of multiple myeloma metastatic to bone that HS1793 “dramatically decreased” lytic skull and femur lesions in treated mice, compared with mice treated with a vehicle placebo, and increased survival of the mice that received the AKT inhibitor.

They also showed that HS1793 was cytotoxic to multiple myeloma cells but not to normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” they wrote.

The study was supported by grants from the Korean government. The researchers reported having no potential conflicts of interest.

SOURCE: Song IS et al. Cancer Lett. 2018;432:205-15.

A novel inhibitor of AKT pathway signaling showed significant cytotoxic activity in mouse models and in human cells isolated from patients with primary or relapsed multiple myeloma (MM), investigators reported.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The experimental agent, labeled HS1793, is a derivative of the naturally occurring antioxidant compound resveratrol. In preclinical studies, HS1793 was shown to offer “great promise in eliminating MM cells and improving therapeutic responses in primary and relapsed/refractory MM patients,” according to Jin Han, MD, PhD, of Inje University in Busan, South Korea, and colleagues.

In a series of experiments, described in the journal Cancer Letters, the investigators demonstrated that HS1793 decreased AKT signaling to induce mitochondria-mediated cell death in multiple myeloma cells, and was cytotoxic and specific for myeloma cells in a mouse model of human metastatic myeloma, and in samples of human multiple myeloma cells.

When activated, AKT promotes oncogenesis by in turn activating other downstream pathways involved in proliferation or survival of malignant cells.

“AKT is frequently activated in MM cells and the incidence of AKT activation correlates positively with disease activity,” the authors noted.

They first screened 400 compounds, and narrowed in on resveratrol analogs, eventually choosing HS1793 as the most promising candidate.

This first experiment found evidence that suggested that the compound inhibits AKT activation by interfering with the interaction between AKT and its promoter HSP90.

They then showed in human MM cell lines that the antimyeloma action of HS1793 appeared to be from a dose-dependent effect that allowed for mitochondria-mediated programmed cell death.

In a separate series of experiments, they found that the inhibition by HS1793 of AKT/HSP90 interaction results in cell death by suppressing nuclear factor kappa–B (NF-KB) pathway signaling. The investigators had previously reported that a different compound, an inhibitor of spindle protein kinesin, induced MM cell death via inhibition of NF-KB signaling.

Next, the investigators showed that HS1793-induced cell death was caused by the direct inhibition of AKT that in turn suppressed NF-KB activation.

Finally, they showed in a mouse model of multiple myeloma metastatic to bone that HS1793 “dramatically decreased” lytic skull and femur lesions in treated mice, compared with mice treated with a vehicle placebo, and increased survival of the mice that received the AKT inhibitor.

They also showed that HS1793 was cytotoxic to multiple myeloma cells but not to normal plasma cells isolated from patients with MM.

“Given that HS1793 treatment specifically induced the death of primary and relapsed MM cells, HS1793 offers excellent translational potential as a novel MM therapy,” they wrote.

The study was supported by grants from the Korean government. The researchers reported having no potential conflicts of interest.

SOURCE: Song IS et al. Cancer Lett. 2018;432:205-15.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

Photo by Rhoda Baer

Experts have published updated guidelines on antimicrobial prophylaxis for adults with cancer-related immunosuppression.

The guidelines include antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions, such as hand hygiene, that may reduce infection risk.

The guidelines were developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA) and published in the Journal of Clinical Oncology.

For the most part, the expert panel that created these guidelines endorsed the previous ASCO recommendations, published in 2013.

However, the panel considered six new studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Recommendations

The ASCO/IDSA guidelines say health care providers should systematically assess the risk of febrile neutropenia, taking into account patient-, cancer-, and treatment-related factors.

Fluoroquinolone prophylaxis is recommended for patients at high risk of febrile neutropenia or profound, protracted neutropenia. This includes most patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and patients undergoing hematopoietic stem cell transplant (HSCT) who are treated with myeloablative conditioning regimens.

Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk of profound, protracted neutropenia, which includes HSCT recipients and most patients with AML/MDS.

However, neither antifungal nor antibiotic prophylaxis are routinely recommended for patients with solid tumors.

Prophylaxis with a nucleoside analog, such as acyclovir, is recommended in patients who are herpes simplex virus–seropositive and are undergoing allogeneic HSCT or leukemia induction.

Pneumocystis jirovecii prophylaxis, such as trimethoprim-sulfamethoxazole, is recommended for patients receiving chemotherapy regimens associated with a greater than 3.5% risk for pneumonia from P jirovecii.

Treatment with a nucleoside reverse transcription inhibitor, such as entecavir or tenofovir, is recommended for patients at high risk of hepatitis B virus reactivation.

Yearly influenza vaccination with an inactivated quadrivalent vaccine is recommended for all patients undergoing chemotherapy for malignancy as well as their family members, household contacts, and health care providers.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce the risk of pathogen transmission, according to the guidelines.

The guidelines also note that outpatients who develop neutropenia following cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores.

The guidelines do not recommend interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks. “Evidence of clinical benefit is lacking” for those interventions, the expert panel said.

Members of the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

[email protected]

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

[email protected]

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

[email protected]

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Commission (EC) has approved a new indication for daratumumab (Darzalex®).

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

Daratumumab was previously approved by the EC for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is EC-approved as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

Preexisting osteoporosis is an important risk factor for mortality risk in cancer-free postmenopausal women who go on to develop multiple myeloma, results of a recent analysis suggest.

©eranicle/Thinkstock

High fracture risk was associated with an increased risk of death, independent of other clinical risk factors, in this analysis of postmenopausal women in the Women’s Health Initiative (WHI) data set.

The findings help define osteoporosis as an important prognostic factor associated with mortality in postmenopausal women who develop myeloma, according to study author Ashley E. Rosko, MD, of Ohio State University, Columbus, and her colleagues.

“Osteoporosis is highly prevalent in aging adults, and very little is known on how this comorbid condition contributes to outcomes in individuals who develop myeloma,” wrote Dr. Rosko and her coauthors. Their report is in the journal Clinical Lymphoma, Myeloma and Leukemia.

The analysis involved 362 women in the WHI data set who developed myeloma and had no history of any cancer at baseline. Women in the WHI were between 50 and 79 years of age and postmenopausal at baseline when originally recruited at 40 U.S. centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for women in the data set using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Of the 362 women who developed myeloma, 98 were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture, or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, according to investigators, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P = .044) versus women with low FRAX scores.

Of the 362 patients who developed myeloma, 226 died during the follow-up period. That included 71 women with high FRAX scores, or 72% of that subset; and 155 women with low FRAX scores, or 59% of that subset, investigators reported.

These findings suggest osteoporosis is an “important comorbidity” in women who develop multiple myeloma, Dr. Rosko and her coauthors said in a discussion of the study results.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” they said.

This investigation was supported in part by the National Cancer Institute. The researchers reported having no relevant financial disclosures.

SOURCE: Rosko AE et al. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):597-602.e1.

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.