No abstract

Attention to signs and symptoms is the foundation for preventing these emergencies or managing additional escalation of symptoms.

Recently, lenalidomide and low dose dexamethasone were found to result in superior overall survival compared to lenalidomide and high dose dexamethasone. The immune suppressive effects of dexamethasone can antagonize lenalidomide immunomodulatory activity and may explain this observation. We conducted a retrospective analysis to evaluate the single agent activity of lenalidomide in newly diagnosed myeloma. Records of patients with newly diagnosed symptomatic multiple myeloma treated with single agent lenalidomide at H. Lee Moffitt Cancer Center and Roswell Park Cancer Institute were reviewed. Data were collected on disease characteristics, demographics, and treatment outcomes. Responses were assessed as per the International Myeloma Working Group criteria. From March 2007 to July 2009, 17 patients with newly diagnosed multiple myeloma were treated with single agent lenalidomide at both institutions. The median age was 70 years (range 46–84 years). Lenalidomide was generally well tolerated and no grade 4 hematologic toxicities were noted. The overall response rate ( partial remission) to lenalidomide alone was 47% at a median follow-up of 7 months (range 1–26). This experience suggests that lenalidomide alone can induce an anti-myeloma effect in previously untreated patients who are considered poor candidates for concurrent dexamethasone.

Background: Elotuzumab (elo), an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7, CD319) has shown activity in combination with dexamethasone and lenalidomide (len) or pomalidomide (pom), in patients with relapsed/refractory (RR) multiple myeloma (MM) in the ELOQUENT 2 and 3 trials, respectively. However, patients enrolled on those trials were not refractory to len or pom respectively and the impact of prior daratumumab (dara) (which can deplete natural killer (NK) cells) was not evaluated. We reviewed the outcomes of RR MM patients treated with elo in combination with either len or pom with respect to prior exposure and refractoriness to IMIDs and dara. Methods: We retrospectively evaluated patients with RR MM who were treated at Moffitt Cancer Center between January, 2017 and July, 2019 with elo in combination with len (elo/len) or pom (elo/pom). We assessed prior therapies and refractoriness to IMIDs and dara. Response was evaluated using the International Myeloma Working Group (IMWG) criteria with added minimal response. Grade 3/4 toxicities were reviewed. This study was approved by the Institutional Review Board. Results: Thirty six patients were identified: 14 on elo/len and 22 on elo/pom. Patient characteristics are outlined in the table. As expected, patients that received elo/pom were more heavily pre-treated, than those who received elo/len, with a median number of 6 prior lines of therapy. The median number of cycles was 9 (range, 2-33) and 3 (range, 1-8) for the elo/len and elo/pom groups, respectively. 21/22 (95%) patients in the elo/pom pts were pom-refractory, whereas 11/14 (79%) of the elo/len patients were len-refractory. For elo/len, the overall response rate (ORR) was 42%, and the median progression-free survival (PFS) was 7.7 months (95% confidence interval, 1.99-10.95, p=0.026) although the ORR was 28.6% in len refractory patients. For elo/pom, the ORR was 14% (for pom refractory patients the ORR was 9.1%) and the median PFS 3.7 months (95% confidence interval, 1.27-6.13 p=0.026). Twenty-three patients (64%) were refractory to dara, with a median time from dara to elo of 13.7 (range, 0.7-33.6) months. Overall survival (OS) and PFS based on the median time from dara to elo were not statistically different. The same analysis based on a 6 months cutoff (assuming shorter dara impact on NK cells) yielded similar results. Thirteen patients remain on treatment at the time of this analysis. Reasons for treatment discontinuation were progressive disease (PD) in 22 (95.7%), adverse event (AE) in 1 (4.3%). Grade 3/4 toxicities were noted in two patients; one patient developed pneumonitis, and another developed infectious complication. Conclusion: The combination of elo with an IMID, such as len or pom, is well tolerated. Elo/IMIDs regimen have modest efficacy in len and pom refractory patients respectively. The timing of and prior dara does not appear to impact the efficacy of elo based therapy. Prospective studies are needed to confirm these findings. Disclosures Shain: Adaptive Biotechnologies: Consultancy; AbbVie: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Alsina:Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau. Baz:AbbVie: Research Funding; Merck: Research Funding; Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding.

5142 Background: The combination of an alkylating agent and bortezomib has been shown to be synergistic both preclinically and in the clinical arena. Although the combination of cyclophosphamide, bortezomib and corticosteroids (CyBorD) has been evaluated by several investigators, many have used different doses and schedule of cyclophosphamide and an optimal schedule has not been established. Herein, we report the safety and efficacy of this combination in patients with relapsed and refractory multiple myeloma. Methods: All patients with myeloma that received this schedule of CyBorD at the Moffitt Cancer Center were included. CyBorD was comprised of cyclophosphamide 1000 mg/2 IV on Day 1, Bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, and 11 and either low dose dexamethasone (equivalent of 120– 160mg/cycle) or prednisone (100 mg PO day 1–5). Demographic, laboratory and clinical data was collected and evaluated via descriptive statistics. Response and progression are defined as per the IMWG uniform response criteria. Results: A total of 20 patients were identified and included for analysis. Demographic data is shown in table 1. At baseline, 35% of patients were platelet transfusion dependent, and the median ß2m was 6.2mg/L. 8 patients (40%) received prophylactic GCSF and 9 patients (45%) received secondary GCSF after significant neutropenia was noted. Overall response rate (PR and better) was 50% (70% minimal response and better), including 1 complete response (CR) and 5 very good partial response (VGPR). Median progression free survival was 3.4 months (95% CI 0–7.5 months) and median overall survival was 11.9 months (95% CI 3.3–20.0). The incidence of grade 3/4 neutropenia and thrombocytopenia was 80% and 75%, respectively. Grade 2 and 3 peripheral neuropahty developed in 1 and 1 patient respectively. Nine patients required dose reductions of cyclophosphamide (only 2 of the 8 who received prophylactic GCSF therapy) and 3 patients required dose reductions of the bortezomib. Conclusion: In this cohort of patients with high burden of disease, intermediate dose cyclophosphamide administered once every 3 weeks in combination with standard dose and schedule of bortezomib results in a meaningful response rate (albeit short PFS) with mainly hematologic toxicities that are manageable with growth factor support. Disclosures: Off Label Use: Cyclophosphamide in combination with bortezomib for relapsed/refractory multiple myeloma. Finley-Oliver:Millenium: Speakers Bureau. Alsina:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allergan: Research Funding. Djulbegovic:Millenium: Research Funding. Baz:Millenium: Research Funding, Speakers Bureau; Celgene: Research Funding.