Outcomes of Myeloma Patients with Deletion 1p Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) Therapy
Authors: Odikadze Levani , Joseph Nisha , Schmidt Timothy M. , Heffner Leonard , Hofmeister Craig C , Dhodapkar Madhav V , Gupta Vikas A. , Boise Lawrence H. , Jaye David L. , Lonial Sagar , Nooka Ajay K , Kaufman Jonathan L 
Published: October 2019

Abstract
Introduction: Previous studies indicated that 1p deletion (del 1p) in multiple myeloma patients has a negative effect on overall survival (OS) and progression free survival (PFS). However, majority of studies were conducted before the introduction of current first line therapy of Lenalidomide, Bortezomib and Dexamethasone (RVD). Our study investigated the association between del 1p and clinical outcomes in patients with MM treated with RVD.
Methods: Single-center, retrospective analysis of an IRB approved myeloma database of 1000 newly diagnosed multiple myeloma patients treated with RVD induction therapy per Richardson et al (Blood 2010), planned stem cell transplant and risk adapted maintenance (Nooka et al, Leukemia, 2014). 1p deletion status was determined by FISH. The primary outcomes were response to RVD, response to ASCT, progression free survival (PFS), and overall survival (OS). Treatment responses were evaluated as per IMWG Uniform Response Criteria.
Results: We identified 1000 multiple myeloma patients who started RVD treatment from July 2005 to August 2016. Among these, 83 patients (8.3 %) were found to have 1p deletion on FISH. The remaining 917 patients formed the control group. Median age at diagnosis, sex and race were similar between groups. Patients with del 1p were more likely to have IgA isotype compared to controls (28.1% vs 19.7%, P=0.054). There was no significant difference between groups in baseline hemoglobin, calcium, platelet count, creatinine and albumin levels. Baseline LDH levels were more likely to be high in the del 1p group (P=0.009). 49.6% of del 1p patients had high risk status (t(4:14), t(14:16), 17p deletion) vs 26.6% in the control group (p<0.0001). There was no significant difference in the best response to induction therapy between groups, with an achievement of a VGPR or better in 62.8% vs 69.3% in the del 1p and control groups respectively (p=0.148). However, the del 1p group had lower best response after transplant, with a VGPR or better in 67.1% vs 89.2% respectively (P<0.001). Univariate regression analysis also showed a significant association of del 1p with decreased PFS (HR 1.782, P=0.002), which stayed significant after adjusting for disease stage, high risk FISH and maintenance (HR 2.265, p<0.001). There was no statistical decrease in OS in the del 1p population.
Conclusion: This analysis demonstrated that the del 1p continues to be associated with adverse outcomes in the era of uniform induction therapy with RVD, transplant and risk-adapted maintenance. There was no significant difference in response to induction treatment, however, del 1p was a significant independent adverse prognostic factor for best response and PFS after ASCT. The lack of decrease in OS may be due to the routine use of risk adapted maintenance.

Disclosures
Heffner: Genentech: Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Research Funding; ADC Therapeutics: Research Funding. Hofmeister:Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Lonial:Amgen: Research Funding. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kaufman:Roche: Consultancy; Abbvie: Consultancy; Karyopharm: Other: data monitoring committee; Janssen: Consultancy; BMS: Consultancy.