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M. Bellei et al.
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Discussion
The International TCP represents the largest cohort of prospectively collected data on patients with aggressive T- cell lymphomas and accurately reflects outcomes for patients treated according to standards of care around the world. In the present study, we sought to analyze the out- comes of patients with relapsed and refractory disease after failure of first-line therapy and to explore potential prognostic factors influencing survival, retrieved from this database. We demonstrated that the outcomes are worse for patients with refractory disease and that the SAR at three years for these patients was only 21%. We also found that late relapse and consolidation with HCT were associated with a longer survival in chemotherapy sensi- tive patients.
In our analysis, refractory/relapsed patients presented a poor risk profile. Sixty-nine percent of failing patients were refractory to first-line treatment and 80% of refrac- tory and 70% of relapsed patients had advanced stage dis- ease at diagnosis. Fifty percent of refractory and 33% of relapsed patients were at high risk according to the Prognostic Index for T-cell lymphoma (PIT); 50% and 32% of relapsed and refractory patients, respectively, were at high-risk according to the International Prognostic Index (IPI).
Survival was poor in our cohort, with a median SAR for refractory and relapsed patients of only 5 and 11 months, respectively. The results from this prospective cohort con- firm findings from other reports that refractory disease is a poor prognostic factor.7,8 While late relapse occurring after 12 months versus early relapse at less than 12 months from front-line therapy was associated with a longer sur- vival, only 11% of patients were in the late relapse catego- ry as most relapses occurred within one year from front- line therapy. Surprisingly, there was no difference in out- comes for refractory/relapsed patients with respect to PTCL subtype, suggesting that significant improvements are needed in treatment strategies for all subtypes of
Figure 4. Survival after relapse (SAR) by salvage therapy including or not hematopoietic cell transplantation (HCT). Elig: eligible; Not elig: not eligible; CR: complete remission; PR: partial remission.
PTCL. We were surprised to find similar survival rates between relapsed and refractory PTCL patients at three years post completion of therapy. However, further analy- sis showed that within the first 24 months of follow up relapsed patients had superior survival, and it is only past that time point that the advantage disappeared. These results suggest that within a category of relapsed patients there is a subgroup with biologically refractory disease and current definitions based on clinical responses are not sensitive enough to identify individuals that would benefit from alternative approaches rather than standard salvage protocols. Furthermore, only about half of the refractory PTCL patients exhibited clinical high risk based on IPI or PIT scores at diagnosis. Emerging genome-wide analysis at diagnosis and/or relapse might overcome these restric- tions and provide a better guide for initial and salvage therapy in the near future.
In the relapsed and refractory setting, the best chance of long-term remission and best outcomes occurred in patients with late (>12 months) relapse who were able to undergo HDT followed by HCT, with SAR at three years of 48%. However, a major problem remains: only 16% of the patients could proceed to this strategy as part of the salvage treatment due to refractoriness to induction thera- py, early relapses, ineffective salvage therapies, and overall poor performance status and patient-specific factors. Two recent population-based retrospective studies focusing on the outcome of relapsed or refractory PTCL patients have been published and they reported a similar poor outcome (median survival after relapse of 5.5 months and 2.5 months).7,8 Likewise, the outcome was far superior in patients able to receive a transplant. Taken together, the current challenge remains to increase the response rates of induction therapies to raise the number of eligible patients for the most effective available intent-to-treat treatment. Moreover, these results highlight the urgent need for novel agents and more effective salvage therapies.
Advances in understanding the biology and genetics of T-cell lymphomas have led to the identification of several
haematologica | 2018; 103(7)