Outcome of 17p Deleted Multiple Myeloma (MM) in the Era of Novel Agents and Tandem Transplantation: A Single Centre Experience
Authors: Parmar Gurdeep , Masih-khan Esther , Atenafu Eshetu G , Reece Donna E. , Trudel Suzanne , Tiedemann Rodger E. , Kukreti Vishal , Chen Christine I. 
Published: October 2019

Abstract
Background:
Although overall MM survival has improved in recent years, there is significant heterogeneity, with some patients achieving survival over 10 years, and others succumbing to disease within months of diagnosis. The presence of cytogenetic abnormalities, in particular deletion 17p (del17p), remains a robust and independent prognostic marker. Although novel agents (single or in combinations) and/or tandem transplantation have been studied in myeloma patients with del17p, results are inconsistent and no regimen has clearly emerged as superior. With this background, we report the outcome of MM patients with del17p treated in the era of novel agents and tandem transplantation at our institution.
Methods:
Using a prospectively maintained MM database, we identified 66 patients with del17p established by non-selective FISH on bone marrow samples, treated at our institution between 2006-2013. Of these, 44/66(66.6%) underwent stem cell transplant. A retrospective chart review of patient, disease, and treatment characteristics, including response and survival outcomes was performed. Prior to 2009, standard therapy at our institution for patients with del17p was a single transplant and tandem transplant was offered only if response rate was less than VGPR. From 2009 on, tandem transplantation was established as our institutional treatment policy for this high-risk subgroup. In this analysis, we aimed to evaluate the outcome of all del17p patients who underwent transplantation and compared single versus tandem transplant outcomes resulting from our policy change.
Results:
Table 1 shows the patient characteristics and outcomes of the 44 patients with del17p who underwent transplantation at our centre.
Patient and disease characteristics: The median age for all patients was 61 (range 31-71 years). High risk features such as elevated LDH, ISS stage II/III and coexistent t(4;14) were seen in 21/44 (48%), 29/42 (69%) and 6/43 (14%) of del17p patients, respectively. Aggressive clinical manifestations such as extra-medullary plasmacytomas and plasma cell leukaemia at diagnosis were seen in 8/44 (18%) and 4/44 (9%) of patients, respectively.
Treatment characteristics and response: 34/44 (77%) patients were treated with bortezomib-based and 4/44 (9%) with lenalidomide-based induction therapy. Of the 44 patients, 23/44 underwent single and 21/44 underwent tandem transplant. The response rate (³VGPR) increased from 54% post chemotherapy to 98% post transplant. A total of 35/44 (80%) patients received maintenance therapy with the majority (77%) given lenalidomide. Median duration of maintenance therapy was 7.6 months (range 1- 56.8)
Survival outcomes: The median follow-up was 23.6 months (1-95 months). Median overall survival (OS) was not reached but 5 year estimated survival rate for all del17p patients who underwent transplantation was 59% (CI 36-76%) and median progression free survival (PFS) was 29 months (CI 20.2-46.1). In a subgroup analysis, estimated 5 year OS rate in patients who received tandem vs single transplant was 65% and 53% respectively (p=0.3). Similarly, the PFS in patients who underwent tandem vs single transplant was 46 vs 28 months, respectively (p=0.1).
Conclusions:
1. The median OS and PFS of del17p myeloma patients treated with novel agents and high dose therapy in our study is comparable to other reported outcomes (e.g., HOVON-65).
2. There was a statistically non-significant trend towards improved OS and PFS in patients receiving tandem transplant when compared to single transplant. Prospective clinical studies are required to clarify this issue.
Table 1: Clinical characterstics Median Range Number (%) Male 25/44 (57) Female 19/44 (43) Age (years) 61 31-71 IgG 22/44 (50) IgA 9/44 (20) Light chain only 8/44 (19) Hemoglobin (g/l) 105 60-147 Creatinine(umol/l) 104 42-561 Serum LDH (U/L) 205 92-710 Beta-2 microglobulin 4.4 1.2-44.8 ISS stage I 13/42 (31) ISS stage II 15/42 (35.7) ISS stage III 14/42 (33.3) 13 q deletion 29/43 (67.4) t(4;14) 6/43 (14) BM nucleated cells with 17p deletion (%) 25 10-74 CR 35/44 (80) VGPR 8/44 (18) PR 1/44 (2) Median time to transplant (months) 5.1 2.5-24 Maintainance treatment received 35/44 (80) Disease progressed 22/44 (50) Deaths 11/44 (25)

Disclosures
Off Label Use: Lenalidomide maintenance therapy after ASCT. Reece:Janssen: Honoraria; Celgene: Honoraria. Trudel:Oncoethix: Research Funding; Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria. Kukreti:Celgene: Honoraria. Chen:Janssen: Honoraria; Celgene: Honoraria.