The Combination of Isatuximab with Pomalidomide and Dexamethasone in Second Line Relapse and Refractory Multiple Myeloma

Introduction: The most impressive data obtained from CD38 targeting immunotherapies-based regimens were observed when used as early as possible in the MM disease course, in second line if not offered in line 1. CD38 targeting immunotherapies, Isatuximab and Daratumumab, are approved in the relapse-refractory Multiple Myeloma (RRMM) setting in triplet-based combinations with pomalidomide (P) and dexamethasone (IsaPd and DPd), however with very limited data in line 2 with IsaPd.

Methods: We conducted a multicenter review study of the patients with second line RRMM treated with CD38 targeting immunotherapies-based regimens with pomalidomide and dexamethasone backbone, IsaPd. Eligible patients were to be adult RRMM in second line, refractory to lenalidomide upfront, naïve to pomalidomide, not refractory to CD38 immunotherapy upfront. The primary endpoint of the study was median PFS. All patients received isatuximab + pomalidomide + dexamethasone until progression as per the approved regimen according to the EU approval.

Results: We recruited 35 patients,median age 72 years old (IQ 67;76), 10 (28%) ISS3, 18 (62%) RISS2-3, 8 (22%) had plasmacytomas', 5 (14%) had PCL features, 4 (11%) HR according to IMS new definition (del17 at the threshold of 50%), 6 (16%) had ASCT upfront. The patients received a median of 12 (IQ 5;20) cycles of IsaPd. At 35.4 (CI95% 35;39.5) months median follow-up, 19 (51%) relapsed and 13 (35%) died. The median PFS was 22.4 (CI95% 13.8-nr). The median OS was nr, projected 40 months was 64% from start of IsaPd. All pre-specified HR definitions had a shorted PFS median time.The median relative dose intensity in IsaPd was >90%, similar to either drug. The safety profile is consistent with the approved IsaPd in ICARIA study.

Conclusions: IsaPd reported prolonged PFS median in second line in lenalidomide refractory RRMM.This study confirms IsaPd as a standard of care for second line RRMM patients.

Perrot:Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Menarini Stemline: Honoraria; GSK: Honoraria.