Maintenance (MT) treatment (Tx) after lenalidomide, bortezomib, and dexamethasone (RVD) induction and stem cell transplant (SCT) in high-risk (HR) patients (pts) with newly diagnosed multiple myeloma (NDMM): A real-world analysis.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e20041-e20041
Author(s):  
Rafael Fonseca ◽  
Kejal Parikh ◽  
Brian Ung ◽  
Quanhong Ni ◽  
Amit Agarwal
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 445-445 ◽  
Author(s):  
Joseph R. Mikhael ◽  
Craig B. Reeder ◽  
Edward N. Libby ◽  
Luciano J. Costa ◽  
P. Leif Bergsagel ◽  
...  

Abstract Abstract 445 Background: Carfilzomib is a proteasome inhibitor that irreversibly binds its target and has a favorable toxicity profile that has shown significant activity in relapsed multiple myeloma (MM), leading to recent FDA accelerated approval. To achieve rapid and deep response in patients eligible for stem cell transplant, we combined carfilzomib with the regimen of cyclophosphamide-thalidomide-dexamethasone (CTD). We recently reported the results of the Phase I component of the trial (in which no MTD was reached) followed by the initial Phase II trial; however, with increasing evidence for the safe and effective use of higher doses of carfilzomib, we now report results from dose escalation extension of the Phase II trial. Methods: Newly diagnosed myeloma patients intended for stem cell transplant were eligible. All patients were treated on a 28 day cycle with Carfilzomib IV Days 1,2,8,9,15,16 (see Table 1 below for dosing per cohort) along with Cyclophosphamide 300 mg/m2 PO Days 1,8,15, Thalidomide 100 mg PO Days 1–28 and Dexamethasone 40 mg PO Days 1,8,15,22. We initially conducted a Phase I run in trial of 6 patients with no DLT observed before expanding to the Phase II portion of the study. The initial phase II regimen is shown below – as no DLTs were observed, we have now fully accrued to the Phase II dose level +1. Treatment was for 4 cycles with expected SCT post induction. The primary endpoint of the trial is the proportion of patients who have ≥very good partial response (VGPR) to treatment. All patients received herpes zoster prophylaxis and ASA daily. Results: A total of 38 patients have been accrued to the trial, 6 in the initial Phase 1, 21 in the initial Phase II, and the remaining at dose escalated cohorts. We are reporting the 27 patients who have completed therapy and will update with the dose escalated cohorts. Median age was 65 (range 27–74) and 52% were female. ISS Stage was advanced (II-III) in 56%. Best overall response rate during 4 cycles of CYCLONE at dose level 0 is 96%: CR 29%, VGPR 46%, PR 21% (1 pt achieved MR). Adverse events of grade 3 or higher at least possibly related to CYCLONE occurred in 12 (44%). Most commonly reported non hematological toxicities (all grades) included fatigue (67%), constipation (56%), lethargy (41%) somnolence (37%), malaise (30%) depressed level of consciousness (22%); however, grade 3/4 toxicities occurring in >5% were uncommon: thromboembolic event 11%) and muscle weakness (7%). Two cases of pneumonia required hospitalization. Eight patients (30%) developed grade 1 sensory neuropathy; no higher grade or painful neuropathy was evident. There were no cardiac events seen in greater than 5% of patients. Grade 3/4 hematological toxicities included neutropenia (15%) and lymphopenia (7%). All patients advancing to SCT successfully collected stem cells. One patient died on study from pneumonia. Conclusion: The 4 drug CYCLONE regimen is highly efficaceous with a response rate after only 4 cycles of 96% (75% ≥VGPR, 29% CR) at the current dosing level of carfilzomib IV 20/27 mg/m2 in newly diagnosed myeloma. Toxicities are manageable, with only grade 1 neuropathy and minimal cardiac or pulmonary toxicity. Increasing the dose of carfilzomib is feasible and updated results of dose escalated cohorts will be reported at 20/36 and 20/45 mg/m2. Disclosures: Bergsagel: onyx: Membership on an entity's Board of Directors or advisory committees. Stewart:Millennium Pharmaceuticals: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Celgene: Consultancy.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20525-e20525 ◽  
Author(s):  
Tanya Marya Wildes ◽  
Sascha Alexander Tuchman ◽  
Brittany Depp ◽  
Ling Chen ◽  
Keith Stockerl-Goldstein ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4085-4085
Author(s):  
Megan B Sears-Smith ◽  
Lillian Charboneau ◽  
Renju Raj ◽  
R. Eric Heidel

Abstract Introduction: Autologous stem cell transplant (ASCT) is considered standard of care in young and fit patients with newly diagnosed multiple myeloma. ASCT has shown to improve depth of response, progression free survival and overall survival compared to systemic therapy alone in myeloma patients (Harousseau et al. New England Journal of Medicine). Proximity to a stem cell transplant center may influence the utilization of this therapeutic option in transplant eligible multiple myeloma patients. Our cancer center did not have a stem cell transplant program in the 100-mile driving radius. The goal of this study was to assess the referral patterns and utilization of ASCT in newly diagnosed, young (age <65 years) multiple myeloma patients in a setting where patients are lacking proximity to a transplant center. Methods: The study was an IRB-approved retrospective cohort study. Patients between 18 and 65 years of age at the time of diagnosis who were diagnosed with multiple myeloma between January 1, 2014, and December 31, 2020, were included. Data including age at diagnosis, sex, race, zip code, treatment regimen, clinical data-including referral to a transplant center, stem cell collection and transplant-were collected and analyzed. Staging was calculated using lab values at the time of diagnosis or within 2 weeks of starting treatment. Date of diagnosis was defined as the date of bone marrow biopsy confirming systemic disease. All frequency and descriptive analyses were performed using SPSS Version 26 (Armonk, NY: IBM Corp.) Results: There were n = 62 patients that met the study inclusion criteria. Patients were mainly white (86%) and male (58%) with an average age at diagnosis of 55.9 (SD = 6.83) years. All patients (n = 62, 100%) lived at zip codes that were more than 100 miles from the closest transplant center. ISS staging showed 37% (n = 23, 95% CI 25% - 50%), 29% (n = 18, 95% CI 18% - 42%), and 18% (n = 11, 95% CI 9% - 30%) to have stage I, II, and III disease respectively. Twelve patients (n = 12, 19.4%, 95% CI 10.4% - 31.4%) had insufficient data for staging. The most common first line regimens were bortezomib, lenalidomide, and dexamethasone (n = 39, 62.9%, 95% CI 49.7% - 74.8%) and bortezomib, cyclophosphamide, and dexamethasone (n = 13, 21%, 95% CI 11.7% - 33.2%). Most patients (n = 48, 77.4%, 95% CI 65% - 87.1%) achieved a very good partial response or better. Eight (n = 8, 13%, 95% CI 5.7% - 23.9%) patients had refractory disease to first line therapy. Forty-six (n = 46, 74%, 95% CI 62% - 85%) patients were referred for HSCT evaluation, n = 16 (26%, 95% CI 15.5% - 38.5%) patients were not. Of the forty-six (n = 46) patients that were referred, n = 44 (96%, 95% CI 85% - 99.5%) patients had a clinical consultation with the transplant team. Of the entire cohort, n = 36 (58%, 95% CI 44.9% - 70.5%) patients underwent stem cell collection and n = 34 (55%, 95% CI 42% - 68%) patients underwent an ASCT after induction therapy. Conclusions: Our study found that more than one third of young patients with newly diagnosed multiple myeloma did not undergo stem cell collection or stem cell transplant. Lack of geographic access to a transplant center may be a contributing factor to the under utilization of this highly effective therapeutic strategy. Further investigation into interventions to improve ASCT referral and completion rates is imperative for improving outcomes for patients in such geographic locations. Disclosures Raj: Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz pharmaceuticals: Speakers Bureau; Glaxo-Smith Kline: Speakers Bureau.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5026-5026
Author(s):  
Nathan W. Sweeney ◽  
Jennifer M. Ahlstrom

Abstract Background: Patients with multiple myeloma (MM) are uniquely susceptible to viral and bacterial illnesses, including COVID-19, due to their immunocompromised state, age, treatments, and comorbidities. With the advent of COVID-19, changes to treatment were recommended whenever possible, in order to reduce visits to the clinic. The total effect of these changes on cancer patients with multiple myeloma remains unclear. The aim of this project was to assess treatment management by changes to treatment of patients with MM during the COVID-19 pandemic. Methods: We utilized HealthTree ® Cure Hub for Multiple Myeloma (healthree.org) and invited patients with active MM cancer or precursor conditions to participate in an online survey. We analyzed patient responses to questions regarding their myeloma treatments during the COVID-19 pandemic. Results: 978 MM patients participated in the survey between February to June 2021. Since March 2020, 151 patients (15%) either delayed, postponed, or stopped a myeloma treatment because of COVID-19. The four most common treatments were daratumumab (20%), lenalidomide (15%), stem cell transplant (13%) and zoledronic acid (11%). There were 110 patients that canceled a planned myeloma treatment. Of these patients, 55 (50%) canceled a planned chemotherapy, 15 (14%) canceled a stem cell transplant, 1 (1%) canceled radiation and 39 (35%) indicated other. Eight patients replaced an intravenous or subcutaneous treatment with an oral treatment because of COVID-19. There were 9 patients that started a new myeloma treatment because of COVID-19, the most common being daratumumab (44%), ixazomib (22%), lenalidomide (22%) and carfilzomib (11%). Finally, 15 patients had their lenalidomide (50%), steroid (42%) and carfilzomib (8%) dose changed. Conclusions: Our results show that decision-making regarding treatment changes were made on an individual basis and that patients who required a change in treatment were the minority. Aggregating real-world data can provide evidence that despite the changes, patients with MM still received and efficacious treatment and avoided putting these patients at risk or mortality. Disclosures Ahlstrom: Bristol Myers Squibb: Other: Patient Advisory; Janssen: Other: Patient Advisory; Pfizer: Other: Patient Advisory; Takeda: Other: Patient Advisory.


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