Advertisement

Phase II study of dose-attenuated bortezomib, cyclophosphamide and dexamethasone (“VCD-Lite”) in very old or otherwise toxicity-vulnerable adults with newly diagnosed multiple myeloma

Published:February 28, 2017DOI:https://doi.org/10.1016/j.jgo.2017.02.004

      Abstract

      Objectives

      Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD (“VCD-Lite”) in such vulnerable adults with newly diagnosed MM (NDMM).

      Materials and Methods

      Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1.3 mg/m2 subcutaneously, cyclophosphamide 300 mg/m2 and dexamethasone 40 mg orally, all on days 1, 8, and 15 of a 28 day cycle for eight cycles, followed by indefinite, alternating bortezomib and lenalidomide maintenance. Toxicity, overall response rate (ORR), progression-free and overall survival (PFS and OS) were determined. The Cancer and Aging Research Group geriatric assessment (CARG GA) was administered at baseline in an exploratory manner as a predictor of severe toxicity.

      Results

      14 patients went on the study, which was closed early due to slow accrual. Intention-to-treat ORR was 64%. 64% of patients experienced grade ≥3 adverse events, the majority of which were unlikely therapy-related. Median PFS was 24.2 months and OS 29.7 months, with 14%, 36% and 29% of patients discontinuing study drugs due to toxicity, MM progression and other reasons respectively. Baseline CARG GA was successfully completed by all subjects but one.

      Conclusion

      VCD-Lite is a viable option for vulnerable adults with NDMM. CARG GA is feasible. Further studies to optimize therapy and to explore CARG GA as a toxicity predictor are vital.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Geriatric Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Smith B.D.
        • Smith G.L.
        • Hurria A.
        • Hortobagyi G.N.
        • Buchholz T.A.
        Future of cancer incidence in the United States: burdens upon an aging, changing nation.
        J Clin Oncol. 2009; 27: 2758-2765
        • Turesson I.
        • Velez R.
        • Kristinsson S.Y.
        • Landgren O.
        Patterns of multiple myeloma during the past 5 decades: stable incidence rates for all age groups in the population but rapidly changing age distribution in the clinic.
        Mayo Clin Proc. 2010; 85: 225-230
        • Palumbo A.
        • Bringhen S.
        • Rossi D.
        • et al.
        Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial.
        J Clin Oncol. 2010; 28: 5101-5109
        • San Miguel J.F.
        • Schlag R.
        • Khuageva N.K.
        • et al.
        Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
        N Engl J Med. 2008; 359: 906-917
        • Magarotto V.
        • Bringhen S.
        • Offidani M.
        • et al.
        Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma.
        Blood. 2016; 127: 1102-1108
        • Larocca A.
        • Palumbo A.
        How I treat fragile myeloma patients.
        Blood. 2015; 126: 2179-2185
        • Palumbo A.
        • Bringhen S.
        • Ludwig H.
        • et al.
        Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN).
        Blood. 2011; 118: 4519-4529
        • Barlogie B.
        • Mitchell A.
        • van Rhee F.
        • Epstein J.
        • Morgan G.J.
        • Crowley J.
        Curing myeloma at last: defining criteria and providing the evidence.
        Blood. 2014; 124: 3043-3051
        • Niesvizky R.
        • Flinn I.W.
        • Rifkin R.
        • et al.
        Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens.
        J Clin Oncol. 2015;
        • Hulin C.
        • Belch A.
        • Shustik C.
        • et al.
        Updated outcomes and impact of age with lenalidomide and low-dose dexamethasone or melphalan, prednisone, and thalidomide in the randomized, phase III FIRST trial.
        J Clin Oncol. 2016; 34: 3609-3617
        • Reeder C.B.
        • Reece D.E.
        • Kukreti V.
        • et al.
        Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial.
        Leukemia. 2009; 23: 1337-1341
        • Reeder C.B.
        • Reece D.E.
        • Kukreti V.
        • et al.
        Long-term survival with cyclophosphamide, bortezomib and dexamethasone induction therapy in patients with newly diagnosed multiple myeloma.
        Br J Haematol. 2014; 167: 563-565
        • Moreau P.
        • Coiteux V.
        • Hulin C.
        • et al.
        Prospective comparison of subcutaneous versus intravenous administration of bortezomib in patients with multiple myeloma.
        Haematologica. 2008; 93: 1908-1911
        • Bringhen S.
        • Larocca A.
        • Rossi D.
        • et al.
        Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.
        Blood. 2010; 116: 4745-4753
        • Extermann M.
        • Boler I.
        • Reich R.R.
        • et al.
        Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score.
        Cancer. 2012; 118: 3377-3386
        • Hurria A.
        • Togawa K.
        • Mohile S.G.
        • et al.
        Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study.
        J Clin Oncol. 2011; 29: 3457-3465
        • Palumbo A.
        • Bringhen S.
        • Mateos M.-V.
        • et al.
        Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an international myeloma working group report.
        Blood. 2015; 125: 2068-2074
        • Hall W.H.
        • Ramachandran R.
        • Narayan S.
        • Jani A.B.
        • Vijayakumar S.
        An electronic application for rapidly calculating Charlson comorbidity score.
        BMC Cancer. 2004; 4: 94
        • Rajkumar S.V.
        • Harousseau J.-L.
        • Durie B.
        • et al.
        Consensus recommendations for the uniform reporting of clinical trials: report of the international myeloma workshop consensus panel 1.
        Blood. 2011; 117: 4691-4695
        • Greipp P.R.
        • San Miguel J.
        • Durie B.G.
        • et al.
        International staging system for multiple myeloma.
        J Clin Oncol. 2005; 23: 3412-3420
        • Palumbo A.
        • Avet-Loiseau H.
        • Oliva S.
        • et al.
        Revised international staging system for multiple myeloma: a report from international myeloma working group.
        J Clin Oncol. 2015;
        • San-Miguel J.F.
        • Richardson P.G.
        • Sonneveld P.
        • et al.
        Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study.
        Leukemia. 2008; 22: 842-849
        • Moreau P.
        • Hulin C.
        • Macro M.
        • et al.
        VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial.
        Blood. 2016; 127: 2569-2574
        • Durie B.
        • Hoering A.
        • Rajkumar S.V.
        • et al.
        Bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT): results of the randomized phase III trial S.
        Blood. 2015; 126: 25
        • O'Donnell E.
        • Laubach J.P.
        • Yee A.J.
        • et al.
        A phase II study of modified lenalidomide, bortezomib, and dexamethasone (RVD lite) for transplant-ineligible patients with newly diagnosed multiple myeloma.
        Blood. 2014; 124: 3454