Real-World Study Highlights Poor OS in Relapsed/Refractory MCL Following BTK Inhibitor Failure

Real-world results from the retrospective SCHOLAR-2 study provided a benchmark for survival in patients with relapsed or recurrent refractory mantle cell lymphoma who received salvage therapy following failure of initial Bruton tyrosine kinase inhibitor therapy.

Real-world data highlighted that patients with relapsed or refractory mantle cell lymphoma (MCL) for whom Bruton tyrosine kinase (BTK) inhibitors had failed experienced worse overall survival (OS), and provided a benchmark for survival among those who received salvage therapy following initial failure or discontinuation of treatment, according to findings from the retrospective chart review SCHOLAR-2 trial.

Of the 240 patients included in the analysis, the median OS in the overall cohort following initiation of first BTK inhibitor therapy was 14.6 months (95% CI, 11.6-20.0). Additionally, median OS was 23.8 months (95% CI, 18.9-30.1) among 149 patients who received salvage therapy following initial BTK inhibitor use and 5.5 months (95% CI, 3.9-8.2) for 91 patients who did not receive subsequent therapy. The 1-year OS estimates following BTK inhibitor use for patients who received follow-up therapy and those who did not, respectively, were 69.1% and 34.4%, and the 2-year OS estimates were 50.0% and 17.2%.

The international, observational SCHOLAR-2 study reviewed cases involving patients 18 years and older with relapsed or refractory MCL whose diseases progressed following initial BTK inhibitor therapy or who discontinued treatment due to intolerance between July 2012 and July 2018. Patients were enrolled from eligible treatment centers that had inpatient diagnostic and treatment facilities for those with B-cell lymphomas, belonged to a network of oncologists/hematologists who treated patients with B-cell lymphomas, had been operational while treating patients for at least 24 months, and had clinical records available for review.

Among 282 screened patients with relapsed or refractory MCL, 240 met the study eligibility criteria of having received prior BTK inhibitor therapy. Of these patients, 149 received salvage therapy, and 91 did not receive subsequent treatment after initial BTK inhibitor use.

The primary outcome of the study was OS. Secondary outcomes included patient demographics, disease characteristics, and treatment patterns among the patient population.

The median age of 226 patients at initial MCL diagnosis was 68 years (range, 39-92). Most patients were male (74.8%) and had stage IV disease (81.5%). Moreover, the majority had an ECOG performance status of 0 or 1 (88.3%), bone marrow involvement (72.6%), and t(11;14) or cyclin D1 overexpression (92.2%). Additionally, 25.2% of patients had blastoid morphology, 28.5% had presence of B symptoms, 8.4% had a bulky disease, 44.1% had splenic involvement, and 27.4% had extranodal disease.

At the start of the first post-BTK inhibitor period among 149 patients, 35.2% had an ECOG performance status of 2 or higher, 37.0% had blastoid morphology, and 19.0% had bulky disease. Moreover, 70.3% of patients had stage IV disease and 45.0% had bone marrow involvement. Patients in this group received a median of 3 prior lines of therapy (range, 1-11). In total, 2.7% of patients received 1 prior line of therapy, 34.9% received 2, 29.5% received 3, and 32.9% received 4 or more. Patients were on BTK inhibitor therapy for a median of 7.1 months.

The majority of patients received treatment with at least 1 BTK inhibitor regimen (93.8%), although a smaller portion underwent 2 lines (5.8%) and 3 lines (0.4%). Additionally, 1.7% of patients received their first BTK inhibitor in the first line, 35.4% received it in the second line, 28.3% in the third line, 16.7% in the fourth line, 12.1% in the fifth line, and 5.8% in a later line. First BTK inhibitor regimens often included ibrutinib (Imbruvica) monotherapy (87.1%) or combined with other agents (10.4%). Additionally, 2.5% of patients received single-agent acalabrutinib (Calquence). A total of 37.9% of patients did not receive any subsequent treatment after BTK inhibitor therapy. Of the other 149 patients who did receive additional systemic anti-lymphoma therapy, 61.7% received 1 line of treatment, 16.8% received 2 lines of treatment, and 14.8% received 3 lines.

The most common first post-BTK inhibitor treatment was chemotherapy, which was administered in 52.3% of patients with or without antibodies; the most common chemotherapy agents included bendamustine (Treanda) and rituximab (Rituxan) in 15.8%, cytarabine-based regimens in 10.7%, or other agents in 14.8%. A total of 45.0% received targeted therapies with or without antibodies following their first BTK inhibitor, including lenalidomide (Revlimid)–containing regimens in 17.4% of patients, bortezomib-containing regimens in 8.7%, and other targeted therapies in 12.8%. Additionally, 2.7% of patients received radiotherapy as their first post-BTK inhibitor therapy.


Hess G, Dreyling M, Oberic L, et al. Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study. Br J Haematol. Published online October 18, 2022. doi:10.1111/bjh.18519