Elranatamab Elicits Early, Deep Responses in Relapsed/Refractory Myeloma

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Elranatamab led to early and deep responses in patients with relapsed/refractory myeloma who were previously treated with a BCMA-directed therapy.

myeloma cells

Patients with relapsed/refractory multiple myeloma who had received prior treatment with a BCMA-directed therapy experienced early, deep and durable responses thanks to treatment with elranatamab.

Patients with relapsed/refractory multiple myeloma who had received prior treatment with a BCMA-directed therapy experienced early, deep and durable responses thanks to treatment with elranatamab according to a pooled analysis of patients enrolled in the phase 1 MagnetisMM-1 and MagnetisMM-2 and phase 2 MagnetisMM-3 and MagnetisMM-9 trials presented at the 2023 ASCO Annual Meeting this weekend.

The findings showed that at a median follow-up of 11.3 months, 87 patients treated with elranatamab after any prior BCMA-directed therapy achieved an overall response rate (percentage of patients whose disease partially or completely responds to treatment) of 46%. Among the 40 patients who experienced a response, the median time to response was 1.7 months.

Among 59 patients who received a prior BCMA-directed antibody-drug conjugate, the overall response rate was 42.4%. The 36 patients who had prior treatment with a BCMA-directed CAR-T cell therapy achieved an overall response rate of 52.8%. Notably, eight patients received prior treatment with both a BCMA-directed ADC and CAR-T cell therapy.

“These results support elranatamab monotherapy as a treatment option for patients with relapsed/refractory myeloma post–BCMA-directed therapy,” Dr. Ajay K. Nooka said in a presentation of the data. Nooka is a professor and director of the myeloma program in the department of hematology and medical oncology at Emory University School of Medicine and the scientific director of Winship Data and Technology Applications Shared Resource at Winship Cancer Institute of Emory University in Atlanta.

Elranatamab is a bispecific antibody targeting BCMA, an antigen that is overexpressed in multiple myeloma, and CD3, an antigen in the immune system’s T cells.

Data from the MagnetisMM-3 study demonstrated that patients who have not been exposed to a prior BCMA-directed therapy achieved an overall response rate of 61%. At a median follow-up of 14.7 months, the median progression-free survival (time during and after treatment when a patient lives without disease progression) and the median duration of response have not yet been reached.

For the pooled analysis, investigators evaluated the efficacy and safety of the bispecific antibody in patients enrolled in one of the four MagnetisMM trials who received at least one proteasome inhibitor, one immunomodulatory drug, one anti-CD38 monoclonal antibody and one BCMA-directed ADC and/or CAR-T cell therapy.

Among all patients, the median age was 66. Thirteen patients were at least 75 years old, including 12 who received prior treatment with a prior BCMA-directed antibody drug conjugate and one who received a prior BCMA-directed CAR-T cell therapy. Additionally, 47.1% of patients were male, and 64.4% of patients were White; however, race was not reported for 21.8% of patients.

Patients had an Eastern Cooperative Oncology Group (ECOG) performance status — assessing how a disease affects a patient’s daily living abilities — of 0 (29.9%), 1 (65.5%) or 2 (4.6%). Per the Revised Multiple Myeloma International Staging System, 20.7% of patients had stage 1 disease, 50.6% had stage 2 disease, and 23% of patients had stage 3 disease. Disease stage data were missing or unknown for 5.7% of patients.

Furthermore, 65.5% and 24.1% of patients had standard and high cytogenetic risk, respectively. Cytogenetic risk data were missing for 10.3% of patients. Fifty-four percent of patients had extramedullary disease (disease found outside the bone marrow), and extramedullary disease status was missing for 3.4% of patients. Bone marrow plasma cells were less than 50% in 70.1% of patients and this information was missing for 11.5% of patients.

Patients received a median of seven prior lines of therapy, and 81.6% of patients underwent prior stem cell transplant. “This was a heavily pretreated patient population,” Nooka noted.

All patients were triple-class exposed, and 85.1% of patients were penta-drug exposed. Furthermore, 96.6% of patients were triple-class refractory, 55.2% were penta-drug refractory, and 85.1% were refractory to their last line of therapy. Additionally, 62.1% were refractory to prior BCMA-directed therapy, including 54% and 11.5% who were refractory to a prior BCMA-directed ADC or CAR-T cell therapy, respectively.

At data cutoff, the median duration of treatment was 3.5 months, and 39.1% of patients received more than six months of treatment. Twenty-three percent of patients who previously received any BCMA-targeted agent were still receiving elranatamab at data cutoff. Reasons for treatment discontinuation included progressive disease (46%), side effects (11.5%), death (10.3%), lack of efficacy (2.3%) and patient withdrawal/refusal of further treatment (6.9%).

Additional data showed that 50% of responders were still in response at data cutoff. Notably, duration of response data were not yet mature after censoring data for 57.5% of responders. The median duration of response was 17.1 months. The median duration response was 13.6 months and not evaluable for patients who received a prior BCMA-directed ADC or CAR-T cell therapy, respectively.

The median progression-free survival was 5.5 months for all patients, 3.9 months for those given a prior BCMA-directed ADC and 10 months for those given a prior BCMA-directed CAR-T cell therapy. The median overall survival was 12.1 months in the overall population, 12.1 months in patients who treated with a prior BCMA-directed ADC and 12.1 months in patients administered a prior BMCA-directed CAR-T cell therapy.

Safety findings showed that the toxicity profile of elranatamab was similar to findings reported in patients naïve to BCMA-directed therapy who were treated in MagnetisMM-3.

The most common hematologic side effects reported in at least 20% of patients consisted of anemia, neutropenia, thrombocytopenia, lymphopenia and leukopenia. Non-hematologic side effects included cytokine release syndrome, diarrhea, COVID-19-related, decreased appetite, cough, injection site reaction and fever.

Notably, side effects led to death in 23 patients, including 11 due to disease progression, eight due to infections (including five due to COVID-19), three due to septic shock/sepsis and four due to other causes, including pulmonary embolism, fall, cardiac arrest and cardiogenic shock.

Infections were reported in 73.6% of patients, including 26.4% of patients who had grade 3/4 infections and 9.2% who experienced grade 5 (terminal) infections. Additionally, 25.3% of patients experienced COVID-19-related side effects and 6.9% of patients permanently discontinued treatment due to infections.

Regarding cytokine release syndrome, 48.3% of patients had maximum event of grade 1, 14.9% of patients had a maximum event of grade 2, and 2.3% of patients had a maximum event of grade 3. No instances of grade 4/5 cytokine release syndrome were reported. Notably, 9.2% of patients experienced more than one cytokine release syndrome event. In 64 patients who received step-up dosing at 12 mg and 32 mg, any-grade cytokine release syndrome was reported in 60.9% of patients and 1.6% of patients had grade 3 cytokine release syndrome.

The median time to cytokine release syndrome onset was two days and the median time to resolution was also two days. Actemra (tocilizumab) was given to 21.8% of patients who had cytokine release syndrome and 11.5% received steroids. One patient permanently discontinued treatment due to cytokine release syndrome.

Additionally, any-grade neurotoxicity occurred in 5.7% of patients, including 3.4% of patients who had a maximum grade 2 event and 2.3% of patients who had a maximum grade 3 event. Neurotoxicity was reported more than once in one patient. The median time to onset of neurotoxicity was two days and the median time to resolution was also two days. Furthermore, 2.3% of patients received Actemra for neurotoxicity, and 3.5% were given steroids. Neurotoxicity led to permanent treatment discontinuation in two patients.

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