PracticeUpdate: Oncology - Winter 2018

EDITOR’S PICKS 11

Progression-Free Survival at 24 Months and Subsequent Outcomes for Patients With DLBCL Annals of Oncology Take-home message • This analysis of the SEAL database was designed to evaluate outcomes among patients with diffuse large B-cell lymphoma (DLBCL) who had attained PFS at 24 months (PFS24). • Patients treated with rituximab-based chemoimmunotherapy on clinical trials who achieved PFS24 had outcomes similar to those of the age-, gender-, and country-matched background population for 7 years after PFS24. Neil Majithia MD Abstract BACKGROUND Patients with diffuse large B-cell lymphoma treated with first-line anthracycline based immunochemotherapy and remaining in remission at two years have excellent out- comes. This study assessed overall survival (OS) stratified by progression-free survival at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the SEAL collaboration. PATIENTS AND METHODS PFS24 was defined as being alive and progression-free 24 months after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared to each patient's age-, sex-, and country-matched gen- eral population using expected survival and standardized mortality ratios (SMRs). RESULTS 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. 1423 evaluable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI: 30.0-34.4). 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI: 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achiev-

Immune Recognition of SomaticMutations Leading to CompleteDurable Regression in Metastatic Breast Take-home message • In this case study of a patient with chemo-refractory HR-positivemetastatic breast cancer, treatment with tumor- infiltrating lymphocytes reactive against four mutated proteins in combination with IL-2 and checkpoint blockade led to complete durable regression of disease, ongoing for over 22 months. • These results demonstrate a new immunotherapeutic approach for these patients. Abstract Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as mela- noma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithe- lial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7. Adoptive transfer of autologous lym- phocytes that specifically target proteins encoded by somatically mutated genes has mediated sub- stantial objective clinical regressions in patients with metastatic bile duct, colon and cervical can- cers8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lym- phocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-pro- tein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients. Immune Recognition of Somatic Mutations Lead- ing to Complete Durable Regression in Metastatic Breast Cancer. Nat Med 2018 Jun 01;24(6)724-730, N Zacharakis, H Chinnasamy, M Black, et al. www.practiceupdate.com/c/69774 Cancer Nature Medicine

ing PFS24 was 93.1% vs. 94.4%, 87.6% vs. 89.5%, and 80.0% vs. 83.7%, respectively. CONCLUSION Patients treated with rituximab containing anthracycline-based immuno- chemotherapy on clinical trials who are alive without progres- sion at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clini- cally indistinguishable from the age-, sex-, and country-matched background population for seven years after achieving PFS24. Progression-Free Survival at 24 Months (PFS24) and Sub- sequent Outcome for Patients With Diffuse Large B-Cell Lym- phoma (DLBCL) Enrolled on Randomized Clinical Trials. Ann Oncol 2018 Jun 12;[EPub Ahead of Print], MJ Maurer, TM Haber- mann, Q Shi, et al. www.practiceupdate.com/c/69589

VOL. 2 • NO. 3 • 2018