Per new real-world efficacy data presented at the 63rd ASH Annual Meeting & Exposition, isatuximab with pomalidomide and dexamethasone (IsaPomDex) appears to have encouraging overall response and progression-free survival (PFS) outcomes among patients with relapsed/refractory multiple myeloma (RRMM).

Researchers measured overall response rates, PFS, overall survival (OS), and adverse events among patients with RRMM across 24 United Kingdom cancer centers and conducted a 3-month landmark analysis “to assess the influence of pomalidomide and dexamethasone dose intensity, and of myeloma response on survival outcomes.”

The final patient cohort included 107 patients with a median age of 69 years, median (IQR) Charlson Co-morbidity Index (CCI) score was 3 (2-4), 61.7 % had CCI <4 and 80.4% had PS<2. Renal presentation (e-GFR<60 ml/min) in the total cohort was 43%; 28 patients had ISS III staging (from 85 patients with known data), 15 patients had high risk cytogenetics (from 62 patients with known data).

At baseline, a median of 3 prior therapies was reported for participants which included transplant (60.7%), alkylator (99.1%), proteasome inhibitors (99.1%), immunomodulatory drugs (100%), anti-CD38 (4.7%) and histone deacetylase inhibitors (3.7%).

A median of 4 IsaPomDex cycles was administered. Overall response rates for 107 patients was 61.7%, “with responses categorized as: ≥VGPR: 25.2%, PR: 36.5%, SD: 18.7%, PD: 14% and unknown: 5.6%.” Objective response was observed at a median of 2.67 months.

Further significant data points were as follows:

• Median PFS in the total cohort was 10.1 months (95% CI: 6.0-12.5).
• PFS survival probability at 3 months was 82.4% (95% CI: 72.7-88.9).
• Pomalidomide and dexamethasone doses were reduced in 40.2% and 41.1% of patients, respectively.
• Treatment is ongoing in 68.2% of patients and was discontinued in 31.8%.

Reported reasons for discontinuation of treatment were death of any cause (14.9%) and toxicity (1.9%).

Age and comorbidity burden rates were not observed to created statistically significant differences for overall response rates. Further, overall response rates were not statistically lower in the dose-attenuated cohort.

“The 3-month land-mark analysis, used to reduce the risk of survivorship bias, demonstrated no statistical difference in PFS according to dose intensity of pomalidomide (<4mg vs 4mg, log-rank P=.1162) or dexamethasone (<100% vs 100%, log-rank P=.2421),” said the researchers, “but there was a statistically improved PFS in those who achieved ≥PR response (log-rank P=.0005).

Median OS was not reached for for the total cohort, age subgroups, or comorbidity subgroups. OS survival probability measured at 3 months was 87.2%.

Adverse events of any grade were reported in 87.9% of patients, with the most common being neutropenia (65.4%), thrombocytopenia (23.4%), infections (23.4%), anaemia (15.9%), and fatigue (10.3%). Most common grade 3 adverse events experienced by 62.6% of patients were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Eighty total hematological adverse events were observed in 57 patients.

“To our knowledge, this is the first study to describe IsaPomDex outcomes in the real-world,” explained researchers. “It demonstrated encouraging [overall response rates] and PFS outcomes in RRMM in the routine care setting, and these were comparable to ICARIA-MM trial data.”

The researchers noted that close monitoring and dose adjustments are required to manage toxicities and additional research, including extended follow-up of this patient cohort will be beneficial.

Reference:
Djebbari F, Vallance G, Basker N, et al. Efficacy outcomes of isatuximab with pomalidomide and dexamethasone are comparable to (ICARIA-MM) trial data: initial results of a UK-Wide real-world study of relapsed myeloma patients. Poster presented at: 63rd ASH Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.