Treatment of patients with diffuse large B-cell lymphoma

W ostatniej dekadzie odnotowano istotne zwiększenie możliwości terapeutycznych u chorych z chłoniakami rozlanymi z dużych komórek B (DLBCL). W randomizowanych badaniach klinicznych wykazano, że dodanie rytuksymabu do schematu cyklofosfamid, winkrystyna, doksorubicyna, prednizon (CHOP), stosowanego co 3 tygodnie (R-CHOP) przyczyniło się do wydłużenia czasu przeżycia wszystkich badanych grup chorych bez nasilenia toksyczności. Inna strategia, polegająca na skróceniu odstępu pomiędzy kolejnymi cyklami CHOP do 2 tygodni (CHOP-14), również wydaje się możliwa do zastosowania u wszystkich chorych w wieku 18–75 lat, ale prawdopodobnie nie jest bardziej skuteczna niż R-CHOP-21. Strategie zwiększające intensywność dawki są obecnie badane z intencją poprawy wyników leczenia u młodszych chorych z DLBCL o wysokim ryzyku. U chorych w starszym wieku poprawy wyników leczenia można się spodziewać po dołączeniu innych leków do schematu R-CHOP. W przypadku niewystępowania ciężkich chorób towarzyszących jest to wciąż zalecany schemat leczenia w tej grupie wiekowej.In the last 10 years, options for treating patients with diffuse large B-cell lymphoma (DLBCL) have greatly expanded. In randomized clinical studies, the addition of rituximab to cyclophosphamide, vincristine, doxorubicin, prednisone (CHOP) delivered every 3 weeks (R-CHOP) has been associated with improved survival rates, without increased toxicity, in all patient groups studied. Another strategy, giving patients dose-dense CHOP - CHOP every 2 weeks or CHOP-14 - has also been found appropriate for all patients between the ages of 18 and 75 years but probably not superior to R-CHOP-21. Strategies with dose-intense regimens are currently tested for improving the outcome of young patients with poor risk DLBCL. In elderly patients, improvement in outcomes might be caused by the addition of another drug to the R-CHOP regimen. Elderly patients are best treated with R-CHOP if they do not have severe concomitant diseases

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial.

BACKGROUND: Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130), including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. METHODS: Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m(2) romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. RESULTS: Of the 32 patients (25 %) with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment). The longest SD was \u3e3 years in a patient who received maintenance dosing of 14 mg/m(2) on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. CONCLUSIONS: We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. TRIAL REGISTRATION: NCT00426764

Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia

PURPOSE A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure