Multiple Myeloma Standard Dose Versus Fixed Dose- A Comparative Study in Transplant Ineligible Patients

Abstracts myeloma (MM) cells and natural killer (NK) cells. Elotuzumab has shown promising results when combined with immunomodulatory drugs such as lenalidomide (Lonial et al, NEJM 2015) in relapsed/ refractory multiple myeloma (RRMM). We aimed to evaluate the activity of elotuzumab in combination with pomalidomide, a novel drug combination that to our knowledge has no currently published data. Methods: We retrospectively reviewed 12 patients with RRMM, treated with elotuzumab in combination with pomalidomide and corticosteroids between November 2015 and December 2016. Elotuzumab was administered IV at a dose of 10mg/kg weekly for the first 8 doses followed by fortnightly infusions, with pomalidomide 4mg PO daily (range 3-4mg). Corticosteroid therapy consisted of dexamethasone (10 patients) given IV or PO with doses ranging from 4 to 40mg weekly and hydrocortisone (2 patients) 100mg IV prior to elotuzumab infusions. Treatment continued until disease progression or unacceptable toxicity. Results: The median age was 64 years (range 56-78) with a male predominance (66%). The median number of lines of prior therapy was 5 (range 38). All patients were refractory to alkylating agents as well as bortezomib and lenalidomide. Nine (75%) patients had previously received high dose melphalan with autologous stem cell transplantation. Paraprotein subtype included 8 IgG, 1 IgA, 1 lambda light chain, 1 kappa light chain and 1 non-secretory patient. 11 out of 12 (91.7%) patients were initially treated with pomalidomide alone. The median time on therapy prior to addition of elotuzumab was 13 weeks (range 1-32). By IMWG criteria, 3 patients achieved a PR with no complete responders (ORR 25%). Seven (58.3%) patients in the cohort achieved a clinical benefit consisting of 3 PR, 3 MR and 1 SD. Amongst patients achieving a clinical benefit the median PFS was 255 days (range 28-376). Median treatment duration with elotuzumab was 9 weeks (range 3-54). The rates of grade 3 or 4 haematology toxicity found in this cohort were anaemia (50%), thrombocytopenia (50%), lymphocytopenia (83.3%) and neutropenia (66.7%). These rates were not unexpected given this patient population. There were no treatment discontinuations or death attributed to drug toxicity. 6 patients have died, 4 from progressive myeloma and 2 from infection. Conclusions: Elotuzumab in combination with pomalidomide and corticosteroids was a tolerable and active regimen in a population of heavily pre-treated patients with RRMM. Given the potential complementary immunomodulatory effects of this drug combination, further investigation earlier in the disease course is warranted.

PS-150 Multiple Myeloma Standard Dose Versus Fixed Dose- A Comparative Study in Transplant Ineligible Patients Aravindh Sivanandan Anand,1 Vipin Kuriakose2 1

Govt Medical College Thiruvananthapuram, Thiruvananthapuram,

India; 2Government Medical College, Thiruvananthapuram, India

Aim: To assess the efficacy of weekly 1.3mg/m2 versus 2mg flat dose in multiple myeloma with Lenalidomide and low dose steroids.

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16th International Myeloma Workshop March 1-4, 2017

To compare the toxicity profile with respect to Varicella reactivation rate, thrombocytopenia, peripheral neuropathy. RELEVANCE There is no published pharmacological data to support the use of body surface area based dosing of bortezomib in myeloma Methodology: This is a prospective observational single institutional study. 60 patients satisfying the inclusion criteria of Age < 80 years, diagnosed as a case of multiple myeloma according to the international myeloma diagnostic criteria and transplant ineligible were included in the study. Patients receiving fixed dose Bortezomib 2mg i/v once, Lenalidomide 10 mg D1 to D21 with Oral Dexamethasone 40 mg weekly (n¼28) and those receiving Bortezomib 1.3 mg/m2 calculated dose with Lenalidomide 10mg and Oral Dexamethasone 40mg weekly(n¼32) were observed prospectively for efficacy and toxicity. None of the patients received prophylactic Acyclovir for Varicella Zoster. Response assessment was done every 6 monthly as per standard Myeloma working group and toxicity assessment as per NTC version 4. Survival analysis was statistically analysed using the Kaplan Meier curves. Results: Patient characteristics between the two arms were well balanced. There was 100 % objective response in both the arms with 21.8% of patients in the standard dosage arm(ARM A) and 23.3% in the fixed dose arm had complete response(ARM B).66.3 % and 63.3% of patients in ARM A and B respectively had very good partial response (VGPR) to treatment. Eventhough none of the patients received prophylactic Acyclovir only 2 out of the total 60 patients developed Zoster infection.Those 2 patients belonged to the ARM A (p¼0.213). 21.4 % ( 6 out of 28) and 9.38%( 3 out of 32) in ARM A and B respectively developed Grade 3/4 peripheral neuropathy(p¼0.281). Grade 3/4 thrombocytopenia was higher in the ARM A with 21.4 % patients developing the same compared to only 6% in ARM B (p¼0.13). Kaplan Meier estimates for survival at 2 years was 92.2% for ARM A and 91.9% for ARM B. Discussion: In our study the median age was 69 years with 80 percent of patients male(n¼48). The CR and VGPR rates between both arms were similar, impressing the fact that fixed dose 2mg Bortezomib is as efficacious as standard dosing 1.3mg/m2. The toxicity profile of both arms were comparable with fixed dosage arm showing a lesser toxicity with respect to percentage incidence. Intravenous Bortezomib was associated with Grade 3/4 peripheral neuropathy in 9 out of the sixty patients. 2 year survival results were also similar with 92.2% and 91.9% in ARM A and B respectively. Conclusion: Our study albeit with limitations was able to demonstrate that fixed dose 2 mg Bortezomib dosage is as efficacious and better tolerable when compared to 1.3mg/m2 Bortezomib in transplant ineligible multiple myeloma patients.