Lenalidomide Break Possible? Study Shows Hope for MRD-Negative Myeloma

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Minimal residual disease (MRD) negativity was maintained for at least 1 year after stopping lenalidomide (Revlimid) maintenance in patients with multiple myeloma, according to findings from an observational trial (NCT04221178) presented at the 21st International Myeloma Society Annual Meeting.¹

Findings showed that among evaluable patients (n = 39), the MRD-negativity rate at 12 months following the end of maintenance therapy was 85% (95% CI, 64%-94%), including 87% of patients enrolled during stage 1 of the study (n = 15) and 83% of patients enrolled in stage 2 (n = 24).

“Cessation of [maintenance] therapy is feasible in [patients with] 3-year sustained MRD negativity,” lead study author Neha Korde, MD, said during a presentation of the data. Korde is an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York.

During the presentation, Korde explained that although lenalidomide maintenance has been associated with improvements in progression-free survival (PFS) and overall survival in patients with newly diagnosed multiple myeloma after autologous stem cell transplant (ASCT), the continuation of maintenance therapy could affect health-related quality of life (HRQOL) in the form of adverse effects and financial toxicities.

Observational Study Design

To evaluate the effect of halting maintenance therapy, investigators enrolled patients at least 18 years of age with multiple myeloma treated with any number of prior lines of therapy.² To enroll in the study, patients were required to have sustained MRD negativity for at least 3 years during continuous maintenance therapy. An ECOG performance status of 2 or less was also required.

The study excluded patients who were MRD positive at the time of screening; those with plasma cell leukemia or another disorder of plasma cell neoplasm; patients receiving any other treatment for multiple myeloma except for bisphosphonates; those who underwent prior solid organ transplant or had a condition requiring immunosuppressive therapy; and patients who previously underwent allogeneic stem cell transplant.

All enrolled patients stopped maintenance therapy and underwent surveillance for 3 years.¹ During surveillance, patients received serum testing every 3 months, MRD testing via the bone marrow every 6 months, and a PET-CT scan every 12 months.

MRD testing was conducted via multiparametric flow cytometry at a 10^-5 sensitivity.

The primary end point was the rate of sustained MRD negativity at 1 year. Secondary end points comprised HRQOL; sustained MRD-negativity rate at 3 years; PFS, event-free survival, and duration of MRD response; responses to retreatment; and microbiome and immunosurveillance.

Fifteen patients were enrolled in stage 1; if at least 8 of those patients were MRD negative after 1 year of surveillance, 35 additional patients could be enrolled in stage 2.

As of the data cutoff date of August 19, 2024, 46 patients had been enrolled between the 2 stages and had a median follow-up of 24.3 months (95% CI, 20-35). Patients had a median time since diagnosis of 8.1 years (range, 5-20) and a median duration of maintenance therapy of 4.6 years (range, 3-13). The mean age was 63 years (range, 29-77), and 67% of patients were male. Seventy-seven percent of patients had International Staging System (ISS) stage I disease, 21% had stage II disease, and 7% had stage III disease; 1 patient’s ISS stage was not reported.

Seventy-six percent of patients had standard-risk cytogenetics, and risk was not available for 9% of patients. In the 15% of patients with high-risk cytogenetics, 1 patient harbored t(4;14) and t(14;16) translocations; 4 patients had 1q amplifications; and 1 patient had a 1q amplification and a t(4;14) translocation.

Prior induction regimens included VRd (bortezomib [Velcade], lenalidomide, and dexamethasone) in 43% of patients; KRd (carfilzomib [Kyprolis], lenalidomide and dexamethasone) in 24% of patients; daratumumab (Darzalex) plus KRd in 13% of patients; and other in 20% of patients. Forty-three percent of patients underwent prior ASCT, and all received lenalidomide maintenance.

Additional Efficacy Data

Among patients who underwent an MRD assessment after discontinuing maintenance (n = 43), 72% remained MRD negative, and 28% converted to MRD positive. In those who converted to MRD positive (n = 12), 7 patients did not experience clinical disease progression, and the remaining 5 patients had clinical progression. In these 12 patients, 4 had high-risk or not reported cytogenetics. The median time to MRD conversion was 16 months (range, 6-49).

In the 7 patients with asymptomatic, stable, MRD-positive disease without clinical progression, 3 patients remained off therapy at a median follow-up of 6 months since MRD positivity was detected; 2 of these patients were retested and remained MRD positive. The other 4 patients restarted lenalidomide maintenance and had a median follow-up of 14 months since converting to MRD-positive disease; 2 of these patients were retested, and although 1 patient remained MRD positive, the other reconverted to MRD negative.

At 24 months, the MRD-negativity rate was 78% (95% CI, 66%-93%). The 24-month treatment-free survival rate was 81% (95% CI, 69%-96%). Notably, the 24-month MRD-negativity rate was 81% (95% CI, 68%-98%) for patients with standard-risk cytogenetics and 67% (95% CI, 42%-100%) for those with high-risk or not reported cytogenetics (P = .21).

Patients who received lenalidomide maintenance for more than 1600 days experienced a 24-month MRD-negativity rate of 84% (95% CI, 70%-100%) vs 70% (95% CI, 51%-96%) for those who underwent maintenance for no more than 1600 days (P = .12).

“In the future, we look forward to ongoing efforts for QOL assessments [and] immune profiling, including microbiome analysis,” Korde concluded. “We also look forward to further defining phase 3 data from the SWOG 1803/[DRAMMATIC] trial [NCT04071457], which is [randomly assigning patients to] maintenance continuation vs discontinuation in a 2-year MRD-sustained population.”

REFERENCES:

1. Korde N, Hassoun H, Landau H, et al. Maintenance therapy cessation for three-year sustained MRD negative multiple myeloma patients. Presented at: 21st International Myeloma Society Annual Meeting; September 25-28, 2024; Rio De Janeiro, Brazil. Abstract OA-15.

2. Stopping maintenance therapy in people with multiple myeloma in MRD-negative remission. ClinicalTrials.gov. Updated August 16, 2024. Accessed October 2, 2024. https://clinicaltrials.gov/study/NCT04221178