The treatment landscape in Hodgkin lymphoma (HL) has changed significantly in recent years with the FDA approval of 2 immune checkpoint blockade (ICB) therapies and more of these agents are also being tested in HL. “Across multiple tumor histologies, including HL, oncologists have recognized that some patients treated with ICB therapies will experience atypical response patterns,” explains Reid W. Merryman, MD. “For example, some patients may have imaging evidence of progression, but with continued ICB treatment, they later achieve a response or durable disease control.”

Provisional modifications of response criteria have been proposed to permit continued use of programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) or other ICB therapies beyond conventionally defined progression. Despite these criteria, data are lacking on the potential benefits of treatment beyond progression (TBP) in HL.

For a study published in The Oncologist, Dr. Merryman, MD, and colleagues collected data from patients with relapsed or refractory HL who received ICB treatment across 17 academic centers. They reviewed medical records from 64 patients with HL who received standard-of-care or investigational ICB agents and at least one subsequent therapy and progressed while receiving their treatment regimen. In total, 20 patients received TBP (TBP cohort) and 44 stopped ICB therapy at initial disease progression (non-TBP cohort). “Our goal was to characterize outcomes of TBP and its impact on subsequent treatments,” says Dr. Merryman.

Highlighting Key Findings

Among patients who received TBP, researchers examined possible predictors of time-to-next treatment (TTNT), which was defined as time from initial progression on ICB therapy to initiation of a subsequent treatment. Patients who received ICB therapy for longer than 4.7 months prior to initial progression had longer TTNT than those treated for fewer than 4.7 months before initial progression. “Patients receiving TBP rarely achieved an objective response, but many had durable disease control,” Dr. Merryman says. “In fact, 35% of patients receiving TBP did not require a subsequent therapy for more than 1 year. Not surprisingly, we also found that the TTNT was longer for patients in the TBP cohort than for the non-TBP cohort (6.6 months vs 1.4 months).”

Continuing an ineffective therapy beyond progression could have a negative impact on the efficacy of subsequent treatments. As such, the overall response rate and progression-free survival (PFS) of post-ICB treatment was analyzed. Overall and complete response rates to post-ICB treatments were similar for the TBP and non-TBP cohorts. “However, patients in the TBP cohort had improved PFS with subsequent treatment,” says Dr. Merryman. PFS of post-ICB therapy was actually longer in the TBP cohort than the non-TBP cohort, with a median of 17.5 months vs 6.1 months, respectively.

In addition, investigators assessed time to subsequent treatment failure (TTSTF), which was defined as time from initial ICB progression to failure of subsequent treatment. “Patients in the TBP cohort had significantly longer TTSTF than those in the non-TBP cohort (34.6 months vs 9.9 months),” Dr. Merryman says (Figure). “This benefit persisted even after controlling for several potential confounding variables, including the type of treatments patients received after ICB, symptoms at the time of progression, and subsequent transplantation.”

More to Come

Data from the analysis must be confirmed in future research because of the study’s retrospective design, according to Dr. Merryman. “In the meantime,” he says, “our data suggest that TBP with a PD-1 monoclonal antibodies may be a beneficial strategy for selected patients with HL. This strategy might be considered for patients who are clinically stable with asymptomatic progression. Importantly, based on LYRIC criteria, patients receiving TBP should undergo a repeat imaging assessment 8-12 weeks after initial progression to monitor treatment response.”

Dr. Merryman notes that future studies should test the strategy of TBP in a prospective fashion with well-defined eligibility criteria to learn more about the potential benefits of TBP. “Obviously, the ideal approach to clarify the benefits of TBP would be a randomized trial, but this will be challenging to conduct in this relatively small patient population,” he says.

References

Merryman RW, Carreau NA, Advani RH, et al. Impact of treatment beyond progression with immune checkpoint blockade in Hodgkin Lymphoma. Oncologist. 2020 Apr 10 [Epub ahead of print]. Available at: https://theoncologist.onlinelibrary.wiley.com/doi/epdf/10.1634/theoncologist.2020-0040.

Cheson BD, Ansell S, Schwartz L, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128(21):2489–2496.

Younes A, Hilden P, Coiffier B, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 2017;28(7):1436–1447.

Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–3067.

Haverkos BM, Abbott D, Hamadani M, et al. PD-1 blockade for relapsed lymphoma post–allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130(2):221–228.