Leukemia & lymphoma
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Leukemia & lymphoma · Jul 2018
A phase 1 trial of autologous stem cell transplantation conditioned with melphalan 200 mg/m2 and total marrow irradiation (TMI) in patients with relapsed/refractory multiple myeloma.
In this phase 1 study, we tested increasing doses of total marrow irradiation (TMI) in addition to standard intravenous melphalan at 200 mg/m2 (Mel200) in the conditioning regimen prior to autologous stem cell transplant (ASCT) for multiple myeloma (NCT02043847). Twelve patients aged 18-75 with relapsed myeloma were enrolled in the study and received Mel200 and TMI 3 Gy (n = 3), 6 Gy (n = 3), or 9 Gy (n = 6) prior to transplant. There were no grade 4 extra-hematologic toxicities and a maximum tolerated dose was not reached. ⋯ Median progression free survival (PFS) was 449 d and median overall survival (OS) was 966 d. We conclude that TMI at a dose of 9 Gy can be safely combined with Mel200 in therapeutic regimens for autologous transplant. Initial clinical results will prompt a phase 2 study.
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Leukemia & lymphoma · Jun 2018
Multicenter StudyCarfilzomib-dexamethasone versus subcutaneous or intravenous bortezomib in relapsed or refractory multiple myeloma: secondary analysis of the phase 3 ENDEAVOR study.
This is a secondary analysis of the phase 3 ENDEAVOR study comparing relapsed and/or refractory multiple myeloma (RRMM) patients receiving carfilzomib-dexamethasone (Kd) with those receiving subcutaneous (SC) bortezomib with dexamethasone (Vd) or intravenous (IV) Vd. Of Kd-treated patients, 356 Kd were pre-selected (by physician prior to randomization if to be randomized to Vd) for SC Vd (Kd [SC Vd]) and 108 for IV Vd (Kd [IV Vd], respectively. Of Vd-treated patients, 360 received SC Vd and 75 IV Vd. ⋯ Median PFS for Kd (IV Vd) and IV Vd were 22.2 and 8.5 months, respectively. Median PFS was significantly longer and response rates were higher for Kd versus retreatment with bortezomib (SC or IV Vd) and in bortezomib naive patients. Overall, Kd was superior to Vd in RRMM regardless of route of bortezomib administration or prior bortezomib exposure.
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Leukemia & lymphoma · Jun 2018
Survival of patients with CD20-negative variants of large B-cell lymphoma: an analysis of the National Cancer Data Base.
Using records from the National Cancer Data Base, we studied overall survival of CD20-negative variants of diffuse large B-cell lymphoma (DLBCL): primary effusion (PEL, N = 228), plasmablastic (PBL, N = 481), ALK-positive large B-cell (ALK + LBLC, N = 15), and human herpesvirus-8-positive DLBCL (HHV8 + DLBCL, N = 77). Three-year survival was 27% for PEL, 40% for PBL, 34% for ALK + LBCL, and 63% for HHV8 + DLBCL. Compared with unspecified DLBCL, and adjusting for clinical characteristics (including the HIV status), survival was significantly worse for PEL (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.31-1.90), PBL (HR 1.66; 95% CI, 1.41-1.95), and ALK + LBCL (HR, 2.70; 95% CI, 1.27-5.75), but not for HHV8 + DLBCL (HR, 0.89; 95% CI, 0.54-1.45). ⋯ Advanced stage was prognostic for PBL (p = .0002), but not for ALK + LBCL (p = .96), or HHV8 + DLBCL (p = .28). In PEL and PBL survival significantly differed according to primary site. Novel therapeutic approaches are urgently needed for these rare diseases.
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Leukemia & lymphoma · May 2018
Meta AnalysisEfficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials.
Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0.24; 95% CI: 0.19-0.30) and overall survival (HR = 0.58; 0.46-0.73) compared with control treatment. ⋯ However, BCR pathway inhibitors increased the risk of grade 3 and 4 adverse events (AEs; RR = 1.25; 95% CI: 1.08-1.44) and serious AEs (RR = 1.32; 95% CI: 1.17-1.50). AEs causing discontinuation (RR = 1.26; 95% CI: 0.88-1.81) or death (RR = 1.06; 95% CI: 0.72-1.57) were not significantly increased. No statistically significant difference in any aspect of meta-analysis was noted between ibrutinib and idelalisib.