A phase II study of bisantrene in patients with relapsed/refractory acute myeloid leukemia.

OBJECTIVES: To determine the current role of bisantrene, an anthracene with anthracycline-like activity which was shown in earlier studies to be effective therapy in relapsed/refractory acute myeloid leukemia with no discernible cardiotoxicity, in the treatment of patients with R/R AML. METHODS: This phase 2, single-center study (NCT03820908) enrolled adult R/R AML to receive bisantrene (250 mg/m2 daily for 7 days) which was administered via an intravenous infusion over 2 hours on days 1-7. Disease assessment included routine blood work and bone marrow studies. RESULTS: In all, 10 patients were enrolled with a median of 3 lines of prior therapy including seven patients who had relapsed following allogeneic stem cell transplantation. The most frequently reported grade ≥3 treatment-attributed hematologic AE was thrombocytopenia, whereas the most frequently reported grade ≥3 treatment-attributed non-hematologic AE was mucositis. Of the 10 patients, one (10%) achieved a complete remission and three patients achieved a partial remission resulting in an overall response rate of 40%. Next-generation sequencing of patient samples identified a wide array of mutations associated with activated signaling, splicing, and epigenetic modification. CONCLUSIONS: In view of the observed low toxicity, a follow-up study combining bisantrene with complementary anti-leukemic therapy is planned.

Progression of disease within 24 months of initial therapy (POD24) detected incidentally in imaging does not necessarily indicate worse outcome.

Progression of disease within 24 months of initial therapy (POD24) has previously been identified as a predictor of reduced overall survival (OS) for patients with follicular lymphoma (FL). Here we attempt to validate this finding in a retrospective cohort and understand whether the method by which progression is determined, clinically or radiographically, influences POD24 robustness. We reviewed records of 635 patients with FL and included 317 patients in our analysis. POD24 occurred in 21.5% of patients and it was evident that OS was significantly lower in the POD24 group. In multivariate analysis both POD24 and FLIPI were independently associated with inferior OS. POD24 that was detected by incidental routine imaging did not predict reduced OS as opposed to progression that was detected clinically. Although surveillance imaging is generally discouraged in FL, it still is a routine practice by many physicians, and therefore our findings are of significant clinical implications.

PET/CT in Disease Detection and Follow-up of Subcutaneous Involvement in Marginal Zone Lymphoma.

BACKGROUND: The value of positron emission tomography/computed tomography (PET/CT) in the staging and assessment of treatment response in marginal zone lymphoma (MZL) lymphomas remains controversial. We investigated radiologic characteristics of subcutaneous MZL as imaged on PET/CT scans. PATIENTS AND METHODS: From the records of a single medical center, for the years 2008 and 2017, we identified subcutaneous lesions in PET/CT scans of patients with histopathologically confirmed MZL in sites other than subcutaneous tissue. RESULTS: Of 571 scans of 178 patients, subcutaneous lesions were found in 20 (11%). Lesions were located in soft tissue structures, mainly along the lateral aspects of the buttocks, thighs and lower and upper back areas, the flank, and the shoulders. Median lengths of the long and short axes of the lesions were 2.0 (range, 1.1-6.0) cm and 0.8 (range, 0.3-2.0) cm, respectively. Median standardized maximum uptake value was 2.3 (range, 0.9-7.6). In 12 patients (60%), MZL was diagnosed at an early stage; 15 (75%) had lymph node involvement and 10 (50%) extranodal involvement. One had spleen and 2 had cutaneous involvement; none had gastric findings. CONCLUSION: The findings of this study support the usefulness of PET/CT in the detection of subcutaneous MZL as well as in staging and treatment decisions.

Efficacy of Gemcitabine as Salvage Therapy for Relapsed and Refractory Aggressive Non-Hodgkin Lymphoma.

Gemcitabine-based salvage therapy is considered an effective treatment for relapsed and refractory Non-Hodgkin's lymphoma (NHL). We analyzed the outcome of 41 consecutive NHL patients treated with gemcitabine-based regimens between January 2007 and October 2015. Twenty-eight males and 13 females (median age 66.4 years) were included. The median follow-up from gemcitabine initiation was 7.3 months. Thirty patients (73%) had B-cell, and eleven (27%) had T-cell, lymphoma. All patients received a median of 2 prior regimens, of which at least 1 was anthracycline based. Twenty-eight patients (78%) received full-dose while 9 (22%) received reduced-dose regimens. The overall response rate was 37%, with 24% (n = 10) complete response, 12% (n = 5) partial response, and 63% (n = 22) progressive disease or stable disease. The median progression-free survival (PFS) was 47 days (range 12-1,318), the median overall survival (OS) was 1.9 years. Twenty patients (49%) died during follow-up. Grade 3-4 hematological toxicity was reported in 21 patients (51%). Relapsed vs. refractory disease, as well as a response to gemcitabine, predicted better PFS and OS. Use of a full-dose regimen predicted a better OS. Compared to previously published data, we observed less favorable outcomes. The administration of gemcitabine-based therapy as a salvage regimen for patients with relapsed or refractory NHL had limited success. Innovative therapies for these patients are an unmet need.