Risk-Adapted Treatment Approach Produces Durable Remissions in MCL

A risk-adapted treatment approach can produce durable responses in younger patients with mantle cell lymphoma (MCL), according to research presented at the International Conference on Malignant Lymphoma 2023.

The findings suggest that “patients with low-risk mantle cell lymphoma may not need chemotherapy and can achieve durable remissions,” said study presenter Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

The findings come from the phase 2 WINDOW-2 trial (ClinicalTrials.gov Identifier: NCT03710772). The trial enrolled 50 patients aged 65 years or younger (median, 58 years) with previously untreated MCL. Patients were classified as low risk (n=11), medium risk (n=18), or high risk (n=21).

For induction, all patients received ibrutinib and rituximab for 4 cycles, followed by ibrutinib, rituximab, and venetoclax for cycles 5-12. Patients who achieved a complete response were assigned to consolidation according to their risk group.

Patients classified as low risk did not receive any consolidation therapy. Medium-risk patients received 2 cycles of chemoimmunotherapy, and high-risk patients received 4 cycles. Chemoimmunotherapy consisted of rituximab, cyclophosphamide, vincristine, dexamethasone, doxorubicin, methotrexate, and cytarabine (R-HCVAD/MTX-ARA-C).

All patients then began 24 months of maintenance therapy with ibrutinib plus rituximab and venetoclax.

Of 46 evaluable patients, all achieved a complete response to ibrutinib-rituximab-venetoclax induction, which met the study’s primary objective. The median number of cycles of the triplet needed to achieve best response was 8 (range, 2-12) cycles.

The median follow-up was 40.7 months. The median progression-free survival (PFS) was not reached, and the 3-year PFS rate was 86%. The median overall survival (OS) was not reached, and the 3-year OS rate was 86%.

Grade 3-4 toxicities on induction included myelosuppression (4%-10%), fatigue (10%), myalgia (10%), rashes (10%), and mucositis (3%). In the patients who received consolidation, grade 3-4 toxicities included thrombocytopenia (70%), neutropenia (32%), and anemia (24%).

Nine patients developed COVID-19 on study, and 4 patients died from COVID-19.

“Chemo-free ibrutinib-rituximab-venetoclax induced an excellent efficacy and safety prior to chemo consolidation,” Dr Wang concluded.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Wang ML, Lee HJ, Fetooh A, et al. Ibrutinib-rituximab and venetoclax (IRV) followed by risk-stratified R-HYPERCVAD/MTX in young patients with untreated mantle cell lymphoma—phase-II WINDOW-2 trial. ICML 2023. June 13-17, 2023. Abstract 101.