Pembrolizumab Produces a Sustained Response in Patients With Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma

Results from the phase 2 KEYNOTE-170 trial (NCT02576990) found that pembrolizumab (Keytruda; Merck) produces sustained antitumor activity in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL).¹

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The study findings, published in Blood, showed that at a median follow-up of 48.7 months (range, 41.2-56.2), pembrolizumab monotherapy (n = 53) produced an investigator-assessed objective response rate (ORR) of 41.5% (90% CI, 30.0%-53.7%), as well as a 20.8% complete response (CR) rate. The median time to CR was 2.7 months (range, 2.0-5.5) in those who achieved a CR and the median duration was not yet reached (NR; range, 33.7+ to 50.0+).

Further, the median duration of response (DOR) was NR (95% CI, NR-NR) and the estimated rate of continued responders at 48 months was 80.6%. The study showed that no patients who achieved a CR progressed or were administered consolidation stem cell transplant or subsequent therapy.¹

In those who initially experienced a partial response (PR; n = 18), 7 patients improved to a CR, 8 stayed in PR, and 3 showed progressive disease. Median progression-free survival (PFS) was 4.3 months (95% CI, 2.8-13.8), with a 48-month PFS rate of 33.0%. Median overall survival (OS) was 22.3 months (95% CI, 7.3-NR) and 45.3% of patients were alive at 48 months.

The FDA granted pembrolizumab accelerated approval on June 13, 2018, based on findings from KEYNOTE-170 for the treatment of adult and pediatric patients with refractory PMBCL, or those who relapsed after at least 2 previous lines of therapy.²

The open-label, non-randomized trial enrolled adult patients with PMBCL who experienced disease progression following, or who were ineligible for, autologous stem cell therapy (ASCT). All patients enrolled in the trial were administered 200 mg of intravenous pembrolizumab every 3 weeks up to 35 cycles or until disease progression, unacceptable toxicity, or withdrawal.¹ Co-primary endpoints were ORR by blinded independent central review and safety, with secondary endpoints of ORR, DOR, PFS, and OS according to investigator assessment.¹

The median age of enrolled patients was 33 years (range, 20-61). Most of the patients were female (57%), had an ECOG performance status of 1 (57%), and did not undergo prior transplantation (74%).³ The median number of prior lines of therapy was 3 (range, 2-8) and all patients were previously administered rituximab (Rituxan), 32.1% previously received radiation, and 26.4% had prior stem cell transplant.¹

A post-hoc analysis of the trial found that ORR was 25.0% and the median DOR was NR (95% CI, 11.1-NR) among 16 patients with primary refractory PMBCL. Those who did not have primary refractory disease (n = 37) had an ORR of 46.9%, including 11 CRs, and a median DOR of NR (95% CI, NR-NR).

After treatment with pembrolizumab, 7 patients subsequently underwent a stem cell transplant, of whom 5 received autologous transplantation and 2 received an allogeneic transplant. There was 1 patient who progressed following ASCT, 1 patient experienced a PR, 1 patient achieved stable disease, and 3 experienced progressive disease. After allogeneic transplantation, 2 patients achieved a PR.¹

In the overall patient population, 24.5% completed 2 years of treatment with pembrolizumab. The remaining patients discontinued treatment because of disease progression (34.0%), clinical progression (22.6%), adverse effects (AEs; 11.3%), and physician’s decision (5.7%), and 1 patient discontinued before 2 years following CR.

Any-grade treatment-related AEs (TRAEs) were observed in 56.6% of patients. The most common any-grade TRAEs included neutropenia (18.9%), asthenia (9.4%), hypothyroidism (7.5%), fatigue (5.7%), and pyrexia (5.7%). Grade 3 or 4 TRAEs were reported at a rate of 22.6%, including neutropenia (13.2%), asthenia (1.9%), and increased aspartate aminotransferase (1.9%).

Serious TRAEs were reported in 7.5% of patients and 1 patient discontinued treatment because of a serious TRAE; however, no deaths were attributed to TRAEs. Death due to AEs unrelated to treatment occurred in 3 patients, caused by myocardial infarction, cardiac tamponade, and Aspergillus infection.

The study authors concluded that pembrolizumab is a safe and effective treatment, producing durable responses in patients with relapsed/refractory PMBCL.

References

1. Zinzani PL, Thieblemont C, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023;142(2):141-145. doi:10.1182/blood.2022019340
2. FDA approves pembrolizumab for treatment of relapsed or refractory PMBCL. News release. FDA. June 13, 2018. Accessed July 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-treatment-relapsed-or-refractory-pmbcl
3. Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019;37(34):3291-3299. doi:10.1200/JCO.19.01389