significant difference between ABVD and AVD, RT or no RT, presence or absence of a residual mass, or PET score (1-3). The remaining 39 pts with bulky stage II HL and a positive PET2 received BEACOPP. Of the 11 patients receiving RT, there was just 1 progression, despite only 5 reaching conventional CT based CR or CR(u).
Conclusion:With longer follow-up, these RATHL results confirm that the primary study endpoint has been met, reliably excluding a 5% inferior 3 year PFS following de-escalation after a negative interim PET-CT. The omission of bleomycin does not significantly affect PFS or OS in pts with negative PET2. With the caveat that this is a non-randomised subgroup, it appears that in pts with bulky stage II HL, those who achieve a negative PET2 have excellent outcomes without the use of radiotherapy. For those with a positive PET2, escalated therapy with BEACOPP and consolidation RT is effective treatment.
Results: Two hundred thirty-four CD30+ HL patients were treated.Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset (>60 y): 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. We identified 30 long-term responders (patients with a response ≥12 months) of whom 18 are still in CR, 7 with a consolidative SCT, and 11 without any consolidative procedure. Duration of response did not differ who achieved at least PR and then either did or did not undergo consolidative SCT. Overall, the treatment was well tolerated in everyday clinical practice, and the toxicity profile was closely similar to the previously published data; no death has been linked to BV-induced toxicity.
Conclusions:The results of this large retrospective study of 234 relapse/refractory HL in the daily practice support the BV efficacy with manageable toxicity superimposable to the one reported in clinical trials results; in particular, there is the confirmation of the similar activity in different settings, eg, in elderly patients, and of the response duration independently by the transplant consolidation. The relevance of the CR status after 4 cycles and the role of BV as a bridge to ASCT for the chemorefractory patients were also pointed up.
Purpose
Brentuximab vedotin (ADCETRIS®), an antibody–drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization.
Methods
Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF).
Results
There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies.
Conclusion
There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.
inhibition of interleukin-2-inducible T-cell kinase by activating T-helper 1 (Th1) cells (Dubovsky, et al. Blood 2013). We describe the effect of ibr treatment on T-cells and cytokines in pts in the DAWN study.Methods: This was a multicenter, single-arm, phase 2 study of ibr in FL pts with ≥2 prior lines of therapy and progressive disease (PD) ≤ 12 months after CIT regimen. Pts received ibr (560 mg QD) on a 21-day cycle until PD or toxicity. A protocol amendment allowed continued ibr treatment in clinically stable/improving pts with radiological evidence of PD (new lesion/increase ≥50%) to account for as responders, but the cytokines showed a similar trend as nonresponders.
Conclusions:In ibr-responding pts at early time points, T regs were downregulated and Th1-associated cytokines IFN-γ and IL-12 were increased. This shift in T-cell population may be linked to the antitumor response; in nonresponders, these cytokines were decreased but T regs were not. Chemokine changes suggest variation in chemoattraction.These data suggest that immunomodulatory effects of ibr could play a role in its antitumor activity in FL; combinations with other therapies may prove beneficial. UCLA,
Keywords
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.