Clinical Trials Review Confirms Poor Outcomes for Patients With Refractory NHL

In an analysis of patient-level data from four large trial cohorts, researchers reported that patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have poor response rates and short overall survival (OS) – highlighting the impetus for developing more effective therapies for this patient population.

“With many promising therapies under development for refractory DLCBL, there is a need for more precise understanding of the expected response and OS rates with currently available therapies … to establish a benchmark for future studies,” Michael Crump, MD, from the Canadian Cancer Trials Group at Queen’s University in Kingston, Canada, and co-authors wrote. In the report, published in Blood, “[We] confirmed our assumptions built on earlier studies that [these] patients do indeed have poor outcomes, regardless of refractory [status].”

The international, multi-cohort SCHOLAR-1 trial (retroSpeCtive non-Hodgkin LymphomA Research) pooled patient-level data from two phase III trials and two observational cohorts of patients with relapsed/refractory disease, totaling 636 patients.

Patients were included in this analysis if they had refractory disease (with either progressive disease as best response to any line of chemotherapy, stable disease as best response to ≥4 cycles of frontline therapy or 2 cycles of later-line therapy, or relapse ≤12 months post-autologous hematopoietic cell transplantation [AHCT]), or initiated a line of therapy after refractory status. Patients had to have evidence of disease assessment after initiation of therapy, andwere excluded if they had primary central nervous system lymphoma.

The investigators reported that response rates were similar across the four datasets, ranging from 20 to 31 percent, for a pooled objective response rate (ORR) of 26 percent. Rates of complete remission (CR), ranged from 2 to 15 percent, for a pooled CR rate of 7 percent (see TABLE 2).

Pooled response rates by refractory subgroup (either primary refractory, refractory to second- or later-line therapy, and relapsed ≤12 months post-AHCT) ranged from 20 to 39 percent. “Response rates were consistently low across all subgroups, with the lowest rates in the primary refractory and high-risk International Prognostic Index (IPI) subgroups,” the authors noted. “Patients who relapsed ≤12 months post-AHCT had higher response rates (34%) than those in the primary refractory (20%) or secondline therapy or greater groups (26%; p value not reported).”

Only 20 percent of patients across the study cohorts were alive at two years, and OS rates were similar regardless of refractory subgroup. Median OS (estimated from the time salvage therapy for refractory disease was initiated) was 6.3 months (range not provided) in the entire cohort. However, although the researchers observed a higher response rate among patients in the post-AHCT group, median OS in this group was similar to those of the other refractory subgroups (6.2 months for patients who relapsed ≤12 months post-AHCT; 7.1 months for those who were primary-refractory; and 6.1 months for those who were refractory to second- or later-line therapy; p value not reported; see TABLE 3).

When the investigators compared OS outcomes across different patient subgroups, they determined that patients who achieved a CR after last salvage chemotherapy had longer median OS (14.9 months; range not reported), compared with non-responders (4.6 months; range not reported). Median OS was also longer among those who had undergone AHCT (n=180; 14.4 months; range not reported) than those who did not (n=423; 5.1 months; range not reported; p values not reported).

Other factors that were significantly associated with OS included:

  • Eastern Cooperative Oncology Group performance status (0-1 vs. ≥2; p<0.0001)
  • disease stage (I-II vs. III-IV; p<0.001)
  • IPI risk groups (low vs. low-intermediate [p<0.001]; low-intermediate vs. high-intermediate [p<0.1])

“These data are particularly important, because they represent a large number of patients treated in the modern rituximab era, suggesting that even with the availability of multiple rituximab-based regimens, outcomes among patients with refractory DLBCL remain dismal across global centers and trials,” the authors concluded.

“Despite potential differences in patient populations and study design, outcomes were quite homogeneous,” the authors reported. However, the study is limited by its retrospective design and variance among data in the analyzed studies. “For example, the time period of patients’ treatment may influence the applicability of the benchmark to future studies,” they added.

Kite Pharma contributed to the funding of the study.

The authors report receiving funding from Kite Pharma.


Reference

Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 August 3. [Epub ahead of print]

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