Combination Therapy Reduced Risk of Disease Progression or Death by 37% in Relapsed/Refractory Multiple Myeloma

A phase 3 study evaluating subcutaneous (SC) daratumumab plus pomalidomide found that daratumumab plus pomalidomide and dexamethasone (D-Pd) significantly reduced the risk of progression or death by 37% in patients with relapsed/refractory multiple myeloma (RRMM) who had received more than or equal to 1 prior line of therapy versus pomalidomide alone, according to data to be presented at the virtual American Society of Hematology (ASH) conference.

Immunomodulatory drug-based regimens are a standard of care for RRMM, with daratumumab being a CD38-targeted mAB approved for treatment of patients with RRMM. Further, the SC formulation of daratumumab has a similar safety profile as intravenous (IV) daratumumab, with a statistically significant reduction in infusion-related reaction (IRR) rates and a considerably shorter administration duration of 5 minutes.

Eligible patients in the APOLLO study had RRMM and received more than or equal to 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI) and had responded to prior treatment and progressed on or after their last regimen. Patients with only 1 prior line of therapy were required to be refractory to lenalidomide, and prior anti-CD38 or pomalidomide was not permitted.

The patients were randomized 1:1 to Pd ± daratumumab SC, and stratification was based on International Staging System disease stage and number of lines of prior therapy.

All patients received 28-day treatment cycles:

• P: 4 mg QD on days 1-21
• D: 40 mg on days 1, 8, 15, and 22
• D-Pd: daratumumab was given QW for cycles 1-2, Q2W for cycles 3-6, and Q4W thereafter.

Patients received daratumumab IV 16 mg/kg before protocol amendment, whereas after protocol amendment, all patients received daratumumab SC 1800 mg co-formulated with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE drug delivery technology, Halozyme, Inc).

All patients were treated until disease progression or unacceptable toxicity, with the primary endpoint being progression free survival (PFS). Major secondary endpoints included overall response rate, rates of very good partial response or better and complete response or better, measurable residual disease‑negativity rate, overall survival, and safety.

A total of 304 patients from 12 European countries were randomized, with the median range being 67 years of age and 45%/33%/22% patients being ISS stage 1/2/3. Further, 35% had high cytogenetic risk and 11% of patients had received 1PL. Whereas 79.6% of patients were refractory to lenalidomide, 40% of patients were refractory to a PI, and 42.4% of patients were refractory to both.

The median duration of treatment was 11.5 months with D-Pd versus 6.6 months with pomalidomide and the primary analysis performed after 190 PFS events. The study met its primary endpoint of improved PFS, with a hazard ratio of 0.63 representing a 37% reduction in the risk of progression or death in patients treated with D-Pd. The median PFS for the D-Pd versus pomalidomide arms was 12.4 versus 6.9 months, respectively. With a median follow-up of 16.9 months, 99 patients have died, yet survival data are immature with ongoing follow-up occurring.

The most common grade 3 or 4 adverse events (AEs) with a more than 5% difference between D-Pd versus pomalidomide were neutropenia (68% vs 51%), leukopenia (17% vs 5%), lymphopenia (12% vs 3%), febrile neutropenia (9% vs 3%), and pneumonia (13% vs 7%). Median duration of injection was 5 minutes, and rates of study treatment discontinuation occurred due to treatment-emergent AEs were similar for D-Pd versus pomalidomide. The safety profile of D-Pd is consistent with known profiles of daratumumab SC and pomalidomide.

The study observed no new safety concerns, and the IRR rate was very low with a short administration duration. Therefore, convenience for patients was increased and treatment burden was decreased, according to the study. The data indicate that D-Pd is an effective, convenient treatment for patients with RRMM who received more than or equal to 1 prior therapy, including lenalidomide and a PI, according to the study.

REFERENCE

Myeloma/Amyloidosis: Therapy, excluding Transplantation: Relapsed/Refractory Multiple Myeloma. Poster presented at ASH 2020 Virtual Conference.