Second-Line Therapy with ICE Followed by High Dose Therapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Peripheral T-Cell Lymphomas: Minimal Benefit When Analyzed by Intent To Treat.
Authors: Horwitz Steven , Moskowitz Craig , Kewalramani Tarun , Hamlin Paul , Straus David , O’Connor Owen , Noy Ariela , Portlock Carol , Nimer Stephen , Palomba M. Lia , Zelenetz Andrew 
Published: April 2020

Abstract
Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with a poorer prognosis than their B-cell counterparts. Second -line chemotherapy (SLT) followed by high dose therapy and autologous stem cell transplantation (HDT/ASCT) is a common approach to patients (pts) with relapsed PTCL. Reports evaluating this approach have analyzed the outcome of transplanted patients. Our goal was to identify pts with relapsed or refractory disease, treated in a uniform manner, with the intent to induce a remission and proceed to HDT/ASCT.
Patients and Methods: From our ICE database we identified 40 pts with a diagnosis of a mature T or NK lymphoma who received ICE as SLT therapy prior to planned HDT/ASCT. Histologic subtypes were as follows: PTCL NOS (n=15), anaplastic large cell lymphoma (n=11), angioimmunoblastic T-cell lymphoma (n=5), NK/T cell lymphoma (n=4), subcutaneous panniculitis-like T-cell lymphoma (n=2), and one each of hepatosplenic γ/δ T-cell lymphoma, enteropathy associated T-cell lymphoma, and transformed mycosis fungoides. Median age was 48 years (24–73), five pts were ≥ 60 years. Twenty-five men and 15 women were treated. Initial chemotherapy regimens included: CHOP/CHOP-like (n=32), NHL-15 (n=5), and other (n=4). Twenty-two pts responded to their initial therapy and 18 had primary refractory disease. At time of relapse, 24 pts had stage IV disease, 23 had elevated LDH, and 9 had a performance status ≤ 70%. Thirty-one pts had at least one extranodal site. Complete second line International Prognostic Index (IPI) factors (AA stage, LDH, PS) were available for 36 pts. IPI scores were LR (n=3), LIR (n=12), HIR (n=13), and HR (n=8).
Results: All pts received at least one cycle of ICE, 36 received all three planned cycles. Fourteen patients (35%) achieved a complete response, 14 (35%) had a partial response, four (10%) had stable disease, and eight (20%) progressed on therapy. Twenty-seven (68%) pts went on to receive HDT/ASCT. Median follow-up for surviving pts was 45 months (range 7–104). By 3 years, 33/40 (83%) of pts had relapsed with a median progression free survival (PFS) of 6 months from last ICE treatment. Twenty-eight (70%) pts relapsed within 1 year. Neither second-line IPI nor histologic subtype was predictive of continuous remission. Relapsed pts had a superior 3 year PFS compared to primary refractory pts 20% vs 6% (p=0.0005). Despite high relapse rate, 18/40 (45%) of pts were alive at last follow-up.
Conclusion: SLT and HDT/ASCT is a common treatment strategy for pts with relapsed PTCL. However, when examined by intention to treat from initiation of SLT and not from time of transplant few pts have durable benefit from this approach. Despite the high response rate to SLT, consolidation with HDT/ASCT provides little clinically meaningful benefit for most pts. The number of pts alive with other therapies despite early relapse underscores the need to study alternative or maintenance strategies for those who achieve remissions.