Triple Therapies Best, But Revlimid with Dexamethasone Could Work in Some Difficult-to-Treat Myelomas, Study Shows

Although triple therapies with Revlimid (lenalidomide) should be prioritized in patients with relapsed or refractory multiple myeloma (RRMM), combining this therapy with dexamethasone could be effective if the patients respond partially after the first treatment cycle, according to new research.

The study, “Response to First Cycle Is the Major Predictor of Long-Term Response to Lenalidomide and Dexamethasone Therapy in Relapsed and Refractory Multiple Myeloma: Can We Spare Patients the Toxicity and Costs of Additional Agents?,” was published in the journal Clinical Lymphoma, Myeloma & Leukemia.

Although triple therapies, including Celgene’s Revlimid, have shown superior effectiveness than its combination with dexamethasone, most guidelines still recommend this dual treatment as the standard of care for some RRMM patients.

In fact, up to 20% of patients on Revlimid and dexamethasone (Rd) consistently show long-term benefits in clinical trials. As such, identifying patients with better outcomes would help select who could safely receive Rd instead of potentially more toxic and expensive triple approaches.

The team in Spain conducted a multi-center study to address this gap, including all RRMM patients starting Rd from January 2009 to December 2016 at three tertiary care hospitals.

A total of 227 patients were analyzed. The group’s median age was 62 years (range 21–84) and 52% were men. Among 120 patients with available data, 29% had high-risk cytogenetics (chromosomal abnormalities).

Durable response — meaning no disease progression for two or more years — was observed in 63 patients (37%). Disease progression occurred in 194 patients (85%), and 170 (75%) had died after a median follow-up of 3.3 years.

The median number of previous treatment lines was 2.7; 14% of patients had been treated previously with Revlimid and 50% had received an autologous stem cell transplant.

Treatment with Rd lasted for a median of 9.2 months. The overall response rate — meaning a partial response or better — was 75%, with 20% of patients experiencing complete response (disappearance of all cancer signs).

After the first treatment cycle, 43% of patients had achieved a partial response, with those on first-time with Revlimid more likely to experience such improvement at this interval — 49% vs. 19% among those who had received the therapy previously . In turn, patients had to undergo a median of six cycles to achieve complete response.

The majority of patients experienced their most favorable response within the first year of treatment, with 90% obtaining very good or complete response within 12 cycles.

High-risk cytogenetics correlated with lower likelihood of achieving complete response, as only one in 34 patients achieved this outcome. In turn, patients with a partial response after the first cycle were significantly more prone to experiencing durable response.

The period of time without disease worsening was longer in patients previously untreated with Revlimid (0.97 years) than in those who had received this therapy (0.75 years).

Among all factors analyzed, partial response after the first cycle was the best predictor of longer periods without cancer progression, or better progression-free survival (PFS).

The 14 patients with both a partial response after the first cycle and history of a myeloma precursor condition — monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) – had significantly longer PFS (2.84 vs. 0.89 years) and overall survival (5.48 years vs. 2.09 years) than the remaining patients.

Of note, the overall survival in the global group was shorter than usually seen in clinical trials, the scientists noted.

High-risk cytogenetics and no history of MGUS were the only prognostic factors associated with shorter overall survival. Patients who had received only one therapy showed a trend toward longer overall survival.

“Our findings support the notion that a triplet treatment is preferable to a [Rd] doublet for most, if not all, patients, and triplet therapy should always be prioritized,” the team wrote. If dual therapy is to be considered, they added, “then at least a [partial response] should be obtained after the first cycle to maintain double-agent therapy safely.”