PF634 OUTCOMES OF SALVAGE WITH INFUSIONAL REGIMENS DT‐PACE/ESHAP FOR REFRACTORY OR RELAPSED MULTIPLE MYELOMA (MM)
Authors: Ainley L. , Counsell N. , Cheesman S. , Rabin N. , Popat R. , Kyriakou C. , Papanikolaou X. , Mehta A. , Yong K. 
Published: June 2019

Background:

While increasing use of proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) has improved treatment outcomes in multiple myeloma, traditional DNA‐damaging agents are still employed in a subset of patients with refractory and/or aggressive disease to rapidly reduce disease burden. DT‐PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide) and ESHAP (etoposide, prednisolone, cytarabine and cisplatin) are used to treat both primary refractory and relapsed disease, and by allowing the harvesting of peripheral blood stem cells, can serve as a bridge to autologous stem cell transplant (ASCT). The role for such approaches in an era with increasing use of new targeted biologically active agents is unclear.

Aims:

We aimed to define patient and disease features associated with improved outcomes that could guide future treatment decisions in real world practice.

Methods:

We identified a retrospective cohort of MM patients who received ESHAP or a DT‐PACE containing regimen, treated between January 2010 and April 2018. Patient characteristics and outcomes were obtained from electronic patient records. Overall response rate (ORR) was assessed as per IMWG; progression free survival (PFS) and overall survival (OS) were analysed using Cox regression and Kaplan‐Meier methods.

Results:

54 patients were identified: median age 52 years (range 28–72), 35 (65%) male. 38 (70%) had primary refractory disease (Ref) at 6.6 months (1.1–34.0) from diagnosis; 16 (30%) patients had relapsed disease (Rel) at 15.7m (7.5–40.2) from diagnosis and 2.4m (0.1–27.1) from last therapy, after 2 (1–3) prior lines and 6 (38%) had had previous ASCT. 29/35 tested (83%) had high risk genetics, 21/29 (72%) patients were ISS 2/3, and 18 (33%) had extra‐medullary disease. 48 (89%) had received a PI, 36 (67%) had received an IMiD, and 3 (6%) had received neither. 14/15 (93%) of ESHAP patients received 1 cycle and 27/38 (71%) of DT‐PACE patients received 2 cycles, one patient received both. ORR was 53% for ESHAP with 27% CR/VGPR, and 76% for DT‐PACE with 37% CR/VGPR; 14 (37%) Ref patients achieved CR/VGPR compared to 4 (25%) Rel patients, ORR was 71% and 63% respectively. 38 (70%) of all patients proceeded to ASCT. After a median follow‐up of 37.6m: 30 (56%) patients had died, 11 (20%) were alive after progression and 13 (24%) were alive and progression‐free. Median PFS was 7.5m (95%CI 4.6–10.4) and median OS was 16.0m (95%CI 0.6–31.4). There was strong evidence that patients who proceeded to ASCT had longer PFS (HR = 0.10, 95%CI 0.05–0.23, p = 0<0.001) and OS (HR = 0.20, 95%CI 0.09–0.41, p < 0.001) than patients who did not. Ref patients also fared better compared to Rel patients (PFS HR = 0.38, 95%CI 0.19–0.76, p = 0.01; OS HR = 0.46, 95%CI 0.22–0.95, p = 0.04). There was no strong evidence of a difference between ESHAP and DT‐PACE patients (PFS HR = 1.21, 95%CI 0.83–1.76, p = 0.32; OS HR = 1.36, 95%CI 0.88–2.11, p = 0.16). In multivariable analyses, adjusting for other factors of interest, only the association with ASCT remained significant for PFS, as well as for OS (HR = 0.10, 95%CI 0.2–4.2, p < 0.01) alongside ISS disease stage (HR = 3.51, 95%CI 1.31–9.40, p = 0.01). Depth of response to ESHAP/DT‐PACE was associated with PFS (p < 0.001) but not OS (p = 0.61).

Summary/Conclusion:

Our data confirm a role for infusional chemotherapy regimens in the management of poor risk MM, and suggest that patients who benefit most from these regimens are those with primary refractory disease and/or are able to receive ASCT as consolidation following salvage.

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