Bortezomib-Thalidomide-Dexamethasone (VTD) As Salvage Treatment in Patients with Multiple Myeloma Candidates for Transplantation in the Real World

Background

Treatment for Multiple Myeloma (MM) has evolved greatly, ranging from corticosteroids to monoclonal antibodies. In low-resource countries, however, the first-choice treatment is still based on cyclophosphamide-thalidomide-dexamethasone (CTD) regimen, either in patients who are candidates or non-candidates for stem cell transplantation (SCT). In Peru, a few years ago, bortezomib has been introduced as salvage treatment. Bortezomib as salvage treatment has reported 6.22 months of time to progression and combined complete and partial response rates of 38% in pivotal study. ¹

Objectives

To determine the response to treatment to VTD in patients with multiple myeloma candidates to transplant. To determine progression-free survival (PFS) to VTD. To determine the percentage of transplant patients.

Methods

We retrospectively assessed the clinical efficacy and toxicity of VTD (bortezomib 1.3mg/m2 subcutaneously on days 1, 4, 8 and 11; thalidomide 100mg orally on days 1 through 21; dexamethasone 40mg orally on days 1, 2, 4, 5, 8, 9, 11, 12 for three-week cycles), as salvage treatment in patients with relapsed/refractory MM candidate to autologous stem cell transplantation treated at Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, between January 2014 and December 2016. Patients received only one prior treatment and at least 2 cycles of VTD. SPSS program was used for data analysis. Survival outcomes were estimated by Kaplan-Meier Method.

Results

Sixteen patients were found to fulfill the selection criteria. The median age was 52 (39-62), fifty-six percent (n=9) were male. International Staging System III disease was present in 75%. ECOG 1-2 was present in 94%. Ig G and IgA MM were 62.5% and 12.5% respectively; lambda light chain was present in 56.3%. 37.5% of patient had renal impairment. B2µg was >3.5mg/dL in 57% of patients. CTD was the first-line in 94%, with overall response rate (ORR) of 62.5% (complete response (CR) 6.3%, very good partial response (VGPR) 12.5%, and partial response (PR) 43.8%). For VTD regimen the median number of treatment cycles delivered was three (range 2-5), totally 59 cycles. After a median of 14 months follow-up for VTD (range 4-34), the overall response rate was 75%, stringent complete response (SCR) was 18.8% (n= 3), complete response 37.5%, very good partial response 6.3%, and partial response 12.5%. Six out of 16 patients (37.5%) with VTD treatment who were candidates for transplantation finally were transplanted. Among the causes for not undergoing transplantation, infections was 40% (20% (two) of cases were pulmonary tuberculosis, one case (10%) was herpes simplex encephalitis, one case (10%) was probable pulmonary aspergillosis), relapsed disease 40%, renal failure 10%, failure of stem cell collection 10%. Median PFS was 14 months (4-33m). 2-years PFS was 37.5%. 5-years overall survival (OS) was 55%, the median was not reached (18-110m). The most common adverse events for all patients were grade 2 peripheral neuropathy and infections (four infections described above), both in 25%, deep venous thrombosis was not reported. Three deaths was reported (18.75%) all for progression disease.

Conclusion

VTD is an effective treatment in transplant candidates with multiple myeloma who have relapsed after one previous therapy including thalidomide. PFS is superior to Bortezomib pivotal study in relapsed disease. Infectious diseases represent 40% of cause for not undergoing transplantation.

References

1. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487-98.