Study Suggests Unsatisfactory Survival in Elderly Patients After Attenuated Therapy for Mantle Cell Lymphoma

Survival among older patients with mantle cell lymphoma (MCL) is “unsatisfactory” following low-intensity immunochemotherapy, with an overall survival of less than 3 years, according to a retrospective analysis of patients from the United Kingdom and Ireland published in British Journal of Hematology.

Based on these findings, the investigators recommended research into non-immunochemotherapy approaches.

“[MCL] presenting in elderly, unfit patients represents a clinical challenge,” Alexandros Rampotas, MRCP, of the department of hematology at the Oxford University Hospitals NHS Trust, and colleagues wrote. “Front-line ‘attenuated’ or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored.”

The investigators performed an analysis of the medical records of 95 patients with MCL who were deemed unfit for full-dose standard therapies such as ritxuimab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisolone—also known as R-CHOP—or rituximab plus bendamustine. The patients received treatment at 19 different centers across the United Kingdom and Ireland between January 2010 and January 2020. Rampotas and colleagues reviewed 4 courses of therapy: dose-attenuated R-CHOP; rituximab plus cyclophosphamide, vincristine, and prednisolone (R-CVP); rituximab plus chlorambucil; and dose-attenuated rituximab plus bendamustine. The main outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS), toxicity, and overall response.

Patients were a median age of 79 years (range, 58-89). Half (50%) were 80 years of age or older. Overall, the patients had a median Cumulative Illness Rating Scale-Geriatric score of 6 (range, 0–24). The most common therapy was rituximab/chlorambucil (n = 30), followed by dose-attenuated rituximab/bendamustine (n = 24), dose-attenuated R-CHOP (n = 22), and R-CVP (n = 19).

The median OS was 31.4 months (95% CI 19.7-43.2), the investigators reported, while the median PFS was 15 months (95% CI, 8.7-21.2). At 2 years, the PFS rate was 37.3% (95% CI, 26.4%-47.7%); at 3-years, the rate was 22.1% (95% CI 12.3%-31.9%).

Fifty-eight patients died. The most common cause of death was progressive disease (n = 36), followed by infection (n = 8), unknown causes (n = 8), secondary malignancies (n = 2), cardiac event (n = 1), multifactorial causes (n = 1), frailty (n = 1), and bowel perforation (n = 1).

A multivariable analysis found that only 1 clinical factor, blastoid morphology, was associated with inferior PFS (HR, 2.9; P = .001). Higher intensity R-CHOP or rituximab/bendamustine appeared to confer a superior PFS than R-CVP or rituximab/cyclophosphamide (HR: 0.49, P = .02).

Rampotas and colleagues reported that several factors were linked with poorer OS, including the status of disease progression before 24 months (HR, 5.68; P < .001), ECOG performance status (HR, 2.14; P = .004), and blastoid morphology (HR, 4.08; P = .001).

The study was limited by the fact that it was a retrospective, nonrandomized review and contained a small sample size, as well as “potential physician frailty assessment and treatment selection bias, the possibility of unmeasured confounding factors, and potential for medical chart misinterpretation.”

“To our knowledge, we report the largest contemporary series of patients receiving therapeutic intervention for MCL in a cohort considered by their treating physician to be unfit for standard immunochemotherapy in routine clinical practice in the literature,” the investigators wrote. “Our present findings corroborate the limited available data and show survival outcomes in this patient group remain unsatisfactory with a median PFS of only 15 months...Given the poor outcomes described, novel non-chemotherapeutic approaches such as [Bruton tyrosine kinase] or BCL2 inhibitors may improve outcomes.”

Reference

Rampotas A, Wilson M, et al. Treatment patterns and outcomes of unfit and elderly patients with Mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis. Br J Haematol. PublishedMay 8, 2021. doi: 10.1111/bjh.17513