Bendamustine, bortezomib and rituximab produces durable complete remissions in patients with previously untreated, low grade lymphoma.

This Phase II trial evaluated the efficacy of bendamustine, bortezomib and rituximab in patients with previously untreated low-grade lymphoma. Eligible patients had low grade lymphoma with no previous systemic disease treatment. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 intravenously (IV) on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6; bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1·6 mg/m2 IV on days 1, 8 and 15. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments had been conducted. Fifty-four eligible patients were enrolled. The most common grade 3/4 toxicities were leucopenia (28%), neutropenia (30%) and lymphopenia (17%). There were no treatment-related deaths and 1 unrelated death on study (embolic stroke). The overall response rate was 94% for all patients. The median follow-up was 54 months. Kaplan-Meier estimates of progression-free survival and overall survival at 36 months were 75% and 88%, respectively. The treatment regimen was well tolerated and produced high response rates. Further study of this regimen in patients with previously untreated lymphoma is warranted.

Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial.

Importance: Chemotherapy may induce alopecia. Although scalp cooling devices have been used to prevent this alopecia, efficacy has not been assessed in a randomized clinical trial. Objectives: To assess whether a scalp cooling device is effective at reducing chemotherapy-induced alopecia and to assess adverse treatment effects. Design, Setting, and Participants: Multicenter randomized clinical trial of women with breast cancer undergoing chemotherapy. Patients were enrolled from December 9, 2013, to September 30, 2016. One interim analysis was planned to allow the study to stop early for efficacy. Data reported are from the interim analysis. This study was conducted at 7 sites in the United States, and 182 women with breast cancer requiring chemotherapy were enrolled and randomized. Interventions: Participants were randomized to scalp cooling (n = 119) or control (n = 63). Scalp cooling was done using a scalp cooling device. Main Outcomes and Measures: The primary efficacy end points were successful hair preservation assessed using the Common Terminology Criteria for Adverse Events version 4.0 scale (grade 0 [no hair loss] or grade 1 [<50% hair loss not requiring a wig] were considered to have hair preservation) at the end of 4 cycles of chemotherapy by a clinician unaware of treatment assignment, and device safety. Secondary end points included wig use and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and a summary scale of the Body Image Scale. Results: At the time of the interim analysis, 142 participants were evaluable. The mean (SD) age of the patients was 52.6 (10.1) years; 36% (n = 51) received anthracycline-based chemotherapy and 64% (n = 91) received taxane-based chemotherapy. Successful hair preservation was found in 48 of 95 women with cooling (50.5%; 95% CI, 40.7%-60.4%) compared with 0 of 47 women in the control group (0%; 95% CI, 0%-7.6%) (success rate difference, 50.5%; 95% CI, 40.5%-60.6%). Because the 1-tailed P value from the Fisher exact test was <.001, which crossed the superiority boundary (P = .0061), the data and safety monitoring board recommended study termination on September 26, 2016. There were no statistically significant differences in changes in any of the scales of quality of life from baseline to chemotherapy cycle 4 among the scalp cooling and control groups. Only adverse events related to device use were collected; 54 adverse events were reported in the cooling group, all grades 1 and 2. There were no serious adverse device events. Conclusions and Relevance: Among women with stage I to II breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have less than 50% hair loss after the fourth chemotherapy cycle compared with those who received no scalp cooling. Further research is needed to assess longer-term efficacy and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01986140.

A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia.

Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI-WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24-month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high-risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well-tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020-1025, 2016. © 2016 Wiley Periodicals, Inc.

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.

PURPOSE: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. PATIENTS AND METHODS: Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for ≥ 1 year were treated with letrozole (2.5 mg) daily for ≥ 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. RESULTS: The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naïve patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. CONCLUSION: These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.