No molecular-informed personalized therapies are currently available for patients with relapsed/refractory multiple myeloma (MM); however, cytogenetics and next-generation sequencing (NGS) can identify molecular abnormalities to provide guidance for more targeted therapy. Tarek Assi, MD, of Gustave Roussy Cancer Campus in Villejuif, France, discussed his research team’s findings that tumor genotyping is associated with higher response rates and prolonged duration of therapy at the ASH Annual Meeting on December 1, 2018.
Researchers assessed 46 patients with relapsed or refractory MM who were screened for molecular or cytogenetics before enrollment in early clinical trials between 2013 and 2018. The mean patient age was 66 years (range = 52–81 years), and patients received a median of three prior therapies (range = 1–8 therapies).
Researcher used the following molecular screening methods: bone marrow cytogenetics, sanger assays for BRAF screening, or NGS on sorted CD138-positive bone marrow cells. Patients with BRAF V600E mutations received a BRAF inhibitor, whereas patients with t(11;14) mutations received a BCL2 inhibitor.
Prior treatments in the cohort included immunomodulatory agents (n = 46; 100%), alkylating agents (n = 43; 94%), or proteasome inhibitors (n = 44; 95%), and 28 patients (62%) had undergone autologous hematopoietic cell transplant.
The researchers observed potentially actionable targets in 13 patients (28%): 8 (17%) with t(11;14) and 5 (11%) with BRAF V600E mutations. Eight patients (17%) received molecularly oriented personalized therapies, including a BRAF inhibitor alone or in combination with an MEK inhibitor (n = 5) or a BCL2 inhibitor in combination with bortezomib and dexamethasone (n = 3). The remaining 38 patients (83%) received other non-molecularly oriented therapies.
The overall response rate (ORR) was 75% among patients receiving molecularly oriented treatment, including four very good partial responses, one partial response (PR), and one complete response. In comparison, the ORR was just 11% for those receiving non-molecularly oriented therapies, including four PRs (p < 0.0001).
The median duration of treatment was 7.3 months (95% confidence interval [CI] = 0.5–29.0) with molecularly oriented therapies and 2.3 months (95% CI = 1.7–8.0) with non-molecularly oriented therapies (p = 0.009).
The median overall survival was not reached in those receiving molecularly oriented therapies versus 43 months with non-molecularly oriented therapies (p < 0.0001).
In the molecularly-oriented group, the median decrease in serum monoclonal component was –94% (range = –99 to –55) compared to –4% (range = –72 to 967) in the non-molecularly oriented cohort (p < 0.001).
“Accelerating the use of prospective genomics tumor molecular portraits may increase the chances of precision medicine for patients with relapse or recurrent MM,” the authors concluded.