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1843 Upfront 28-Day Metronomic Therapy for High-Risk Multiple Myeloma (HRMM)

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Sharmilan Thanendrarajan, MD1, Daisy V. Alapat, MD2, Maurizio Zangari, MD1, Carolina Schinke, MD1*, Christoph Heuck, MD1, Frits van Rhee, MD, PhD1, Adam Rosenthal3*, Joshua Epstein, DSc1, Shmuel Yaccoby, PhD1, Faith E Davies, MD1, Gareth J Morgan, MD PhD1 and Bart Barlogie, MD, PhD1

1Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR
2Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR
3Cancer Research And Biostatistics, Seattle, WA

Introduction: Despite major advances in MM therapy with the inclusion of novel agent combinations for induction prior to and after autotransplant-supported high-dose melphalan, the 15% of patients with GEP-defined HRMM continue to fare poorly with PFS and OS not exceeding 2 and 3 years, respectively. This poor outcome has not been improved with less dose-intense and more dose-dense Total Therapy 5. Having previously reported on 16-day metronomic therapy with low-dose doxorubicin (DOX) and cisplatin (DDP) plus VTD (Papanikolaou, Haematologica), we explored further extension of such metronomic treatment to 28 days (metro-28) also in newly diagnosed HRMM patients.

Patients and Methods: All patients signed a written informed consent and data analysis was approved by our IRB. In the outpatient setting, a  single cycle of metro-28 comprised DOX and DDP each at 1.0mg/m2/d for 28d by continuous infusion (CI), along with VTD (bortezomib 1.0mg/m2 on days 1-4, 7-10, 13-16, 19-22, 25-28; DEX 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; thalidomide 50-100mg/d x 28d; some patients also received vincristine [VCR] at a flat daily dose of 0.07mg/d x 28d by CI.

Results: Fourteen patients were initiated on metro-28. Their characteristics included age >=65y in 12; albumin <3.5g/dL in 8; B2M >5.5mg/L in 7; cytogenetic abnormalities [CA] were present in 10; GEP70 HRMM in 9/13; PR subgroup in 8/13 (Table 1). The median follow up is 11mo. As portrayed in Figure 1A, no patient has died; the 6mo PFS estimate was 85% (Figure 1B); responses included CR in 3/14, VGPR in 7/14 and PR in 10/14 (Figure 1C); and the PR duration estimate at 6mo is 80% (Figure 1D). Of interest, GEP70 scores morphed to low risk in 3/13. Vascular density (CD34) decreased markedly in most patients evaluated. Toxicities were minor; myelosuppression was virtually absent; alopecia was not encountered. Subsequent salvage therapies included repeat metro-28, combination chemotherapy (PACMED) and autotransplants.

Conclusion: We conclude that metro-28 is a promising and safe strategy for elderly patients with HRMM, and we hypothesize an anti-angiogenic mechanism of action in addition to direct anti-MM effects.

 

Table 1: Patient characteristics

Factor

n/N (%)

Age >= 65 yr

12/14 (86%)

Albumin < 3.5 g/dL

8/14 (57%)

B2M >= 3.5 mg/L

9/12 (75%)

B2M > 5.5 mg/L

7/12 (58%)

Hb < 10 g/dL

10/14 (71%)

Cytogenetic Abnormalities

10/14 (71%)

CA within 1 Year of Therapy

10/14 (71%)

CA within 90 Days of Therapy

9/14 (64%)

GEP 70-Gene High Risk

9/13 (69%)

GEP PR Subgroup

8/13 (62%)

GEP Proliferation Index >= 10

7/13 (54%)

GEP Centrosome Index >= 3

7/13 (54%)

n/N (%):  n- Number with factor, N- Number with valid data for factor

 

Figure 1

Disclosures: Thanendrarajan: University of Arkansas for Medical Sciences: Employment . Alapat: University of Arkansas for Medical Sciences: Employment . Zangari: University of Arkansas for Medical Sciences: Employment ; Onyx: Research Funding ; Millennium: Research Funding ; Novartis: Research Funding . Schinke: University of Arkansas for Medical Sciences: Employment . Heuck: Millenium: Other: Advisory Board ; Janssen: Other: Advisory Board ; Foundation Medicine: Honoraria ; Celgene: Consultancy ; University of Arkansas for Medical Sciences: Employment . van Rhee: University of Arkansa for Medical Sciences: Employment . Rosenthal: Cancer Research and Biostatistics: Employment . Epstein: University of Arkansas for Medical Sciences: Employment . Yaccoby: University of Arkansas for Medical Sciences: Employment . Davies: Janssen: Consultancy ; Onyx: Consultancy ; University of Arkansas for Medical Sciences: Employment ; Millenium: Consultancy ; Celgene: Consultancy . Morgan: MMRF: Honoraria ; Takeda: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; CancerNet: Honoraria ; Bristol Myers Squibb: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Weismann Institute: Honoraria ; Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; University of Arkansas for Medical Sciences: Employment . Barlogie: University of Arkansas for Medical Sciences: Employment .

*signifies non-member of ASH