Gemcitabine and liposomal doxorubicin (GemDox) for the treatment of relapsed and refractory T-cell lymphomas.

Aggressive T-cell lymphomas (TCL) account for 10-15% of non-Hodgkin lymphomas (NHL) with weaker responses and shorter durations to chemotherapy than other types of NHL. Current therapies for patients with relapsed/refractory Cutaneous T-cell lymphoma (CTCL) have limited efficacy, and short durations of response. Gemcitabine and liposomal doxorubicin have shown single-agent activity in TCL and combined have activity in relapsed B-cell lymphomas. We evaluated outcomes of 18 patients with relapsed/refractory aggressive TCL (13 CTCL, 5 PTCL) treated with a gemcitabine plus liposomal doxorubicin (GemDox) combination and evaluated outcomes with a specific focus on CTCL patients. Significant responses were observed in CTCL patients with an overall response rate of over 80%. In all patients, objective responses were seen in eight patients (50%), with six patients (5 CTCL) able to proceed to allogeneic stem cell transplant. Given limited treatment options for r/r CTCL, GemDox should be considered a therapeutic option in relapsed/refractory CTCL.

Real-World Experience of Adults With Acute Myeloid Leukemia on Hypomethylating Agents With or Without Venetoclax at a Comprehensive Cancer Center.

Background: Venetoclax (VEN) in combination with hypomethylating agent (HMA) therapy is a standard treatment option for patients with newly diagnosed acute myeloid leukemia (AML); however, data are limited in the relapsed or refractory (R/R) populations and in those with poor-risk disease. A retrospective review was conducted involving patients with AML who received HMA alone or in combination with VEN (VEN + HMA). Methods: VEN + HMA was compared to HMA alone in first-line and R/R settings. Patients were stratified by specific HMA and line of therapy. The primary endpoint was overall response rate (ORR) up to 6 months from start of treatment. Results: Fifty-two patients were evaluated for efficacy and 78 patients for safety. ORR was 67% (VEN + HMA) versus 80% (HMA) in the first line and 50% versus 22% in R/R setting. A greater clinical benefit was seen with VEN + HMA compared to HMA in both lines of therapy (first-line: 87% vs. 80%; R/R: 75% vs. 67%). The median duration of response was longer with VEN + HMA first-line, but shorter in the R/R setting compared to HMA (8.3 vs. 7.2 months and 2.5 vs. 3.7 months, respectively). Of the 32 patients who responded to therapy, 63% had a complex karyotype. Survival benefits were greater with VEN + HMA in both lines of therapy, although not statistically significant. Grade 3/4 neutropenia was reported in all patients receiving VEN, and 95% of these patients also experienced grade 3/4 thrombocytopenia. There were three cases of tumor lysis syndrome. Conclusion: The addition of VEN to HMA has consistently shown benefit as first-line treatment and may have some benefit in R/R settings as well. Further studies are needed to compare across various lines of treatment and unfavorable disease. Dynamic strategies that improve toxicity management should be considered.

Hypertension and incident cardiovascular events following ibrutinib initiation.

Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including emerging reports of profound hypertension (HTN). The long-term incidence, severity, and impact of HTN development with ibrutinib are unknown. Therefore, in 562 consecutive patients treated with ibrutinib for B-cell malignancies from 2009 through 2016, we assessed the new/incident or worsened HTN (systolic blood pressure [BP] cutoff, 130 mm Hg). Observed incident HTN rates were compared with Framingham-heart-predicted incident HTN rates. We also evaluated the relationship of HTN to the development of other major adverse cardiovascular events (MACEs), including arrhythmia, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the effects of different antihypertensive classes on ibrutinib-related HTN. Overall, 78.3% of ibrutinib users developed new or worsened HTN over a median of 30 months. New HTN developed in 71.6% of ibrutinib users, with a time to 50% cumulative incidence of 4.2 months. Among those without preceding HTN, 17.7% developed high-grade HTN (BP >160/100 mm Hg). In multivariate regression, new or worsened HTN was associated with increased MACEs (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.08-4.38). No single antihypertensive class was associated with prevention or control of ibrutinib-related HTN. However, antihypertensive initiation was associated with a lower risk of a MACE (HR, 0.40; 95% CI, 0.24-0.66). Collectively, these data suggest that ibrutinib is associated with a substantial increase in the incidence and severity of HTN, and that HTN development carries a higher risk of subsequent cardiotoxic events.

Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

OBJECTIVE: The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). METHODS: This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. RESULTS: From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. CONCLUSIONS: The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin.