Longer Revlimid Maintenance after Stem Cell Transplant Prolongs Myeloma Patient Survival

Longer duration of maintenance therapy with Revlimid (lenalidomide) after autologous hematopoietic stem cell transplantation (HSCT) prolongs survival for multiple myeloma patients without increasing their risk of developing other primary cancers, researchers found.

The findings come from the retrospective study “Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma,” published in the journal Cancer.

“Nearly all patients with multiple myeloma who undergo autologous HSCT ultimately experience disease relapse,” Qaiser Bashir, MD, assistant professor of stem cell transplant at the University of Texas MD Anderson Cancer Center, and his colleagues wrote. “It has been well established that post-transplant maintenance therapy can delay the relapse and potentially prolong survival.”

The study investigated previous research on Revlimid that left murky results and unanswered questions.

“Despite promising survival data, many clinicians remain apprehensive about the long-term use of lenalidomide [Revlimid] maintenance because of the unclear association between the duration of maintenance and survival, the increased risk for toxicity and the higher incidence of second primary malignancies,” the authors wrote.

Bashir and colleagues conducted a retrospective study of multiple myeloma patients who began maintenance therapy with Revlimid after receiving high-dose chemotherapy and HSCT between 2007 and 2013 at the university’s cancer center.

The conditioning chemotherapy given to the majority of the patients (85%) before their HSCT was single-agent Alkeran (melphalan). Revlimib maintenance therapy was administered at various doses ranging from 5 mg/day to 15 mg/day.

After a median follow-up of 26.6 months, the researchers assessed the patients’ progression-free survival, overall survival, clinical response, disease progression, and relapse — all defined according to the International Myeloma Working Group response criteria.

Overall, 464 patients with multiple myeloma were included in the study. Patients had a median time to auto-HCT from diagnosis of 7.2 months. Maintenance therapy with Revlimib was started less than 4 months after HSCT in 46% of the study cohort.

The overall response rate after auto-HCT for the 442 patients who responded to maintenance with Revlimib was 97%. But during maintenance therapy with Revlimib 159 patients exhibited improvement, including 86 patients (19%) who achieved complete remission. The overall response rate was 98%.

The results increased the complete response rate from 40% (175 patients) after auto-HCT to 59% (261 patients) with maintenance therapy. The median time to achieving complete response from the start of maintenance was 8.6 months.

The median progression-free survival (PFS) and overall survival (OS) were 38 and 78 months, respectively, for the entire population. Compared to patients with high-risk cytogenetics, those without high-risk cytogenetics had higher median PFS (24.6 months vs. 39.6 months) and OS (67.7 months vs. not reached) rates.

The time of the initiation of maintenance therapy with Revlimib did not affect PFS (31.9 months for early initiation vs. 31.5 months for late initiation) or OS (64 months for early initiation vs. not reached for late initiation). There were no differences in PFS and OS based on whether patients did or did not achieve complete response after HSCT.

The report showed that the duration of maintenance with Revlimib affected the outcomes.

Compared to patients on maintenance therapy for less than two years, those on maintenance for two years or more showed improvements in both PFS and OS, the researchers reported. Specifically, those who stayed on Revlimid for longer than three years had a 98% lower risk of disease progression and a 95% increased overall survival.

Twelve cases of second primary malignancies developed over a median of 2.2 years. The cancers included myelodysplastic syndrome (4 patients), melanoma (2 patients), sarcoma (2 patients). One person each developed acute myeloid leukemia, lung cancer, Hodgkin’s lymphoma, and squamous cell carcinoma of the skin.

The most common reason for discontinuing maintenance therapy was disease progression (143 patients) and adverse events (91 patients).

The researchers noted some study limitations, including its retrospective design, lack of standardization in screening second primary cancers, and lack of complete data from all patients included.

“However, we have conducted an exhaustive analysis of the impact of the duration of lenalidomide maintenance on survival and the incidence of second primary malignancies, and we conclude that conceivably the most practical approach is to continue maintenance lenalidomide until unacceptable toxicity or disease progression after autologous HSCT,” the researchers wrote.

Saad Z. Usmani, MD, director of plasma cell disorders and director of clinical research in the department of hematologic malignancies at Levine Cancer Institute at Carolinas HealthCare System, believes that the study may ease patient fears about extended maintenance therapy and the incidence of second primary cancers.

“Does this study answer any of the major questions posed here? It probably does not, but it may support the notion that lenalidomide maintenance does provide a survival benefit to real-world patients, and there is probably a group of patients who may even benefit from a longer duration of lenalidomide maintenance,” Usmani wrote in an accompanying editorial. “These data will be important in answering most of the questions posed specifically about lenalidomide maintenance.”