Addition of Lenalidomide to SOC Shows Feasibility, Safety in MDS, AML and CMML

Thomas Schroeder, MD

Following allogenic stem cell transplant (allo-SCT), lenalidomide (Revlimid) at a dose of 5 mg a day can be added safely to the standard of care combination of azacitidine (Vidaza) and donor lymphocyte infusions (DLI) as salvage therapy for patients with relapse of myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) with MDS-related changes, results from the phase 2 AZALENA study (NCT02472691) show.¹

The open-label, single-arm, multicenter study investigated the safety and feasibility of lenalidomide in addition to the standard therapy of azacitidine and DLI as first salvage therapy for this patient population.

“We have seen encouraging response rates, duration of response and survival including patients with early and/or hematologic relapse in AZALENA. Azacitidine, lenalidomide and DLI favorable modulated the balance between GvHD and [graft-versus-leukemia; GvL] and is an efficient treatment option for patients with myeloid neoplasms relapsing after allogeneic stem cell transplantation which should be further investigated in randomized trials,” stated Thomas Schroeder, MD, assistant professor, section head, Department of Internal Medicine, Division of Hematology/Oncology, medical director of Radiation Oncology, University of New Mexico, during an presentation of the data at the 48th Annual EBMT Meeting.

AZALENA enrolled 50 participants aged 18-99 with first relapse of de novo or therapy-related MDS, CMML or AML in various participating centers across Germany.² Other requirements for inclusion in the study included possibility of DLI, no previous therapy for relapse after allo-SCT, an ECOG status of 0-2, and no uncontrolled infection at the time of enrolment.

Of the patients enrolled in the trial, the median age was 63 years. Forty-six percent of the patients with AML (n = 23), 48% with MDS (n = 24) and 6% with CMML (n = 3). A majority of patients (72%) were not in remission at the time of transplantation but received standard-dose conditioning (68%).

Patients included in the study received a median of 275 treatment cycles and were given azacitidine as a standard of care at 75 mg for 7 days every 28 days for up to 8 cycles. DLIs were then administered after cycle 4, 6 and 8 at a dose of 5-10x105CD3+/kg (1st DLI), 1-5x106CD3/kg (2nd DLI) and 5-15x106CD3/kg (3rd DLI).

The investigational drug, lenalidomide, was also started on day 1 for 21 days every 28 days for 8 cycles at most. A starting dose of 2.5 mg of lenalidomide per day was given to the first 10 patients. If no dose limiting toxicity was observed at the time of a first interim analysis, the next 10 patients were to be treated with 5 mg per day. In case of no DLT after a second interim analysis, the remaining 30 patients were treated with 5 mg per day.

The primary end point of the study was to evaluate safety including the number, types, and severity of adverse events (AEs), graft versus host disease (GvHD) and hospitalization. The secondary end point of the study examined safety in regard to response, duration of response, and overall survival.

Findings revealed there to be an overall response rate of 56% (n = 28). The time to complete response was 113 days seen in the 50% of patients with a median of 4 cycles. A total of 20 patients with CR had received DLI. Of the patients included, 6% showed a partial response. The median OS for all patients was 21 months and the 1-year OS rate was 65%. Patients who achieved remission had a superior survival versus 9.7 months.

In regard to toxicity, almost a third of the patients had either grade 3 or 4 neutropenia (30%) or thrombopenia (38%) at the time of study entry. Of the 275 treatment cycles, 246 included 89% of patients receiving the combination therapy, and in 29 cycles, lenalidomide was omitted in 5 patients (11%).

Lenalidomide-related AEs which were grade 3 or higher were seen in some patients including 38% of patients (n = 19) having to be hospitalized at some point in the duration of the trial. Grade 3 AEs seen in patients included infections (20%), febrile neutropenia (10%), gastrointestinal disorders (6%), and nervous system disorders (6%). Grade 4 AEs consisted of infections (4%) and febrile neutropenia (2%).

Looking at GvHD, 30% of the patients suffered from acute GvHD and 38% chronic GvHD. Time to GvHD onset was approximately 112 days the majority of patients with GvHD (77%, n = 20) had received DLI.

References:

1. Azacitidine, lenalidomide and DLI as salvage therapy for MDS, AML AND CMML relapse after allogeneic SCT- Final results of the prospective AZALENA-Trial (NCT02472691) Presented at: 48th EBMT Annual Meeting; March 19-23, 2022. Abstract OS07-03. Virtual.

2. Azacitidine, lenalidomide and DLI as salvage therapy for MDS, CMML and sAML relapsing after allo-HSCT (AZALENA). Clinicaltrials.gov. Accessed March 31, 2022. https://clinicaltrials.gov/ct2/show/NCT02472691