To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus ...cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL).
Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program.
After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio HR = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant NS). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003).
As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.
(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation ...(ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6−30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach.
The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known ...about safety and efficacy of KRd outside a clinical trial context.
Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers.
Median age was 62 years; patients had received a median of two previous lines of treatment (range 1-10) and 52% were refractory to previous treatment. Median number of KRd cycles was 12 (2-29), with a mean duration of treatment of 12 months; 21 patients had received at least 18 cycles. Overall response rate was 61%, including 18% complete response. Median PFS was 22.9 months, median OS was not reached. Creatinine clearance >30 mL/min, quality of the best achieved response and standard Fluorescence In Situ Hybridization (FISH) risk were independent predictors of favorable outcome. Patients who received the full-dosage of carfilzomib in the first two cycles had a better outcome.
KRd was effective and well tolerated and in a considerable proportion of patients, therapy continued beyond the 18th cycle. The finding of a better outcome in patients with the higher cumulative dose of carfilzomib in the first two cycle encourages to maintain the maximum tolerated dose.
Objective
The objective of this study was to determine the efficacy of palonosetron combined with dexamethasone in prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in ...patients receiving multiple-day chemotherapy and the efficacy of a second dose of palonosetron in treating breakthrough emesis.
Materials and methods
Forty-six patients treated with multiple-day chemotherapy for hematologic malignancies received palonosetron as prophylaxis for CINV on the first day of chemotherapy and dexamethasone throughout the entire period of chemotherapy. If breakthrough emesis occurred, a second dose of palonosetron was administered after 72 h following the first administration. The results were retrospectively compared to group of patients with similar clinical characteristics undergoing similar multiple-day chemotherapy. This group had received single-dose ondansetron as CINV prophylaxis on the first day of chemotherapy plus dexamethasone throughout the entire period of chemotherapy and metoclopramide for breakthrough emesis.
Results
One hundred eighty and 173 chemotherapy cycles were administered in the palonosetron and ondansetron groups, respectively. Nausea and vomiting were absent in 80% of patients of the palonosetron group and 60% of the control group (
p
< 0.05). In the palonosetron group, 67% of patients who experienced CINV were successfully rescued by a second dose of palonosetron, while in the ondansetron group, only 22% showed a no CINV after metoclopramide treatment (
p
= 0.04).
Conclusions
The present results appear to be encouraging in terms of complete prophylaxis of CINV and treatment of breakthrough emesis in the setting of multiple-day chemotherapy.
Abstract High-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be ...identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m2 ) to high-dose MEL (140 mg/m2 ) before a second ASCT, in a tandem ASCT strategy, in 64 patients with “de novo” MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study.
Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, ...retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment gastrointestinal toxicity (36.3%) and skin rash (10.3%). Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.
Objective and Methods
In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical ...records of 47 patients treated with BvB in second relapse or beyond were reviewed.
Results
The median number of previous treatments was 2 (1‐4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21‐day cycle. The median number of BvB cycles was 4 (2‐7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow‐up of 19 months (5‐47), median PFS was 18 months (95%CI: 23‐29), and the 2‐year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%).
Conclusion
Our real‐world results suggest that BvB is an effective third‐line rescue and bridge‐to‐transplant regimen for RR‐cHL patients.
Summary
High‐dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable ...proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third‐generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR‐HL accrued into a prospective registry‐based study. Application of FEAM resulted in a 2‐year progression‐free survival (PFS) of 73·8% 95% confidence interval (CI), 0·64–0·81 with median PFS, overall survival and time to progression yet to be reached. The 2‐year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12–0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose (18FFDG)‐uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had 18FFDG‐positrin emission tomography‐positive lesions before HDT, the 2‐year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12–0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR‐HL patients typically pre‐exposed to lung‐damaging treatments.
To evaluate activity and safety of obinutuzumab-miniCHOP (Ga101-miniCHOP) combination in older patients with Diffuse Large B-Cell Lymphoma (DLBCL) unfit to receive full dose immunochemotherapy.
We ...conducted a Simon's two-stage phase II multicenter trial to investigate response rate (primary endpoint) and safety of six courses of Ga101-miniCHOP in older patients with DLBCL (≥65 years), prospectively defined as unfit according to a simplified Comprehensive Geriatric Assessment (sCGA).
Overall, 34 patients were enrolled (median age 82 years; range 68–89), with 27 out of the 33 eligible patients completing all six planned courses. Complete Remission (CR) rate was reported in fourteen patients (42%). After a median follow-up of sixteen months, the two-year Progression Free and Overall Survival (PFS and OS) were 49% (95% Confidence Interval (CI), 28 to 67) and 68% (95% CI, 49 to 81), respectively. The most frequent grade 3–4 adverse event was neutropenia in thirteen patients (26%).
Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL.
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