These interim trial results support the ongoing phase 3 ITHACA trial.
Isatuximab (Sarclisa; Sanofi) and lenalidomide (Revlimid; Bristol Myers Squibb) (ISA-LEN) combination was well-tolerated and led to a significant overall response rate (ORR) after 18 cycles of treatment in patients with high-risk smoldering multiple myeloma (HRSMM), according to interim results presented in an abstract at 21st International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro, Brazil.1
Image credit: © Сергей Косилко | stock.adobe.com
Typically, patients with HRSMM have a median time to progression to symptomatic MM of less than 2 years. In these patients, previously conducted phase 3 randomized trials of lenalidomide and LEN-dexamethasone have demonstrated improved progression-free survival (PFS).1
One such trial, conducted by Mateos et al, randomized 119 patients with HRSMM to either observation or treatment groups. At a 40-month follow-up, the median time-to-progression was found to be significantly longer in the treatment group compared with the observation group. Furthermore, the 3-year survival rate was higher in the treatment group.2
Studies like those guided the investigators as they underwent this interim analysis from a phase 2 trial evaluating ISA-LEN in patients with HRSMM (NCT04270409). The primary end point of the trial was ORR after 6 months of ISA-LEN therapy, with secondary end points of PFS, ORR at cycles 18 and 30, and overall survival (OS). The results were reported at the 18-cycle point.1
Thirty-six patients were enrolled in the trial between September 2020 and October 2022, of which 33 had an evaluable response following 18 cycles. ORR was measured to be 94%; interestingly, the depth of response improved in 12 patients (36.4%) between cycles 6 and 18, according to the investigators. At the data cut-off point of March 2022, 2-year PFS was determined to be 97.1% (CI: 91.8%-100%). Median PFS has not yet been reached, and there have been no patient deaths.1
Trial Name: A Phase 3 Randomized, Open-label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma
ClinicalTrials.gov ID: NCT04270409
Sponsor: Sanofi
Completion Date (Estimated): October 2033
Regarding safety, the most frequent hematologic grade ≤ 2 treatment-related adverse events (TRAEs) were leukocytopenia (69%), lymphopenia (58%), anemia (44%), thrombocytopenia (39%), and neutropenia (36%). Some common non-hematologic TRAEs were also experienced, including nausea, fatigue, and diarrhea.1
Isatuximab was recently granted FDA approval in combination with bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed MM who are not eligible for autologous stem cell transplantation. The interim results presented at the IMS annual meeting are poised to contribute to the wealth of continued research on these therapies, including the ongoing phase 3 ITHACA trial, which is evaluating isatuximab in combination with or without lenalidomide and dexamethasone.1,4
The investigators wrote that the ITHACA trial had the potential to change the standard of care in HRSMM and could eventually become one of the many FDA-approved treatments for these multiple myeloma patients.1,4
