Further Evolution of Metronomic Therapy Extended to 28 Days (Metro28) for Relapsed Refractory Multiple Myeloma (RRMM)

Autor: Faith E. Davies, Susan Panozzo, Carolina Schinke, Yogesh Jethava, Xenofon Papanikolaou, Christoph Heuck, Maurizio Zangari, Frits van Rhee, Gareth J. Morgan, Bart Barlogie, Clyde Bailey, Adam Rosenthal, Rashid Z Khan
Rok vydání: 2014
Předmět:
Zdroj: Blood. 124:2128-2128
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v124.21.2128.2128
Popis: Despite the increasing availability of novel agents for RRMM, many patients run out of treatment options due to disease refractoriness and/or progressive toxicities, both hematological (cytopenia) and non-hematological (cachexia, asthenia, renal and cardiopulmonary).Patients who are refractory to both proteasome inhibitors and immunomodulatory agents (IMIDs) carry an ominous prognosis with a median overall survival (OS) of 9 months (Leukemia, Kumar 2013). We previously reported on the efficacy and toxicity profiles of a metronomically scheduled chemotherapy regimen administered over the course of 16 days (Haematologica, Papanikolaou 2014). Encouraged by the results of that treatment, we have since modified metronomic chemotherapy to cover a 28-day period (metro28). The regimen consisted largely of bortezomib 1.0mg/m2 on days 1, 4, 7, 10, 13,16,19, 22,25,28; along with dexamethasone 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; thalidomide 100mg days 1-28, continuous 28 day infusion of doxorubicin 1.0mg/m2 (0.5mg/m2 for Ejection Fraction 2mg/dL), with the addition of arsenic trioxide (ATO) at 0.1mg/kg on each day after bortezomib; and lately vincristine (VCR) at 0.07mg daily dose by continuous infusion for 28 days. Patient characteristics included age >65yr, 46%; female, 33%; cytogenetic abnormalities at any time prior to therapy (CA), 86%; Gene Expression Profile (GEP) 70-defined high risk, 44%. The median number of prior therapies was 8 (1-64), prior transplants, 83% (1, 2, >=3), 20%, 32%, 31%; prior exposure to novel agents including Carfilzomib/Pomalidomide was 81%. Thrombocytopenia prior to treatment was present in 75% including thrombocytopenia Table 1: Patient characteristics at start of Metro28 therapy Factor n/N (%) Age >= 65 yr 56/122 (46%) IgA Isotype 28/110 (25%) Female 40/122 (33%) White 108/122 (89%) Albumin < 3.5 g/dL 47/122 (39%) B2M >= 3.5 mg/L 46/93 (49%) B2M > 5.5 mg/L 26/93 (28%) CRP >= 8 mg/L 54/122 (44%) Creatinine >= 2 mg/dL 15/122 (12%) Hb < 10 g/dL 57/122 (47%) LDH >= 190 U/L 36/121 (30%) Platelet Count < 150 x 10^9/L 92/122 (75%) Cytogenetic abnormalities 105/122 (86%) CA within 1 year of therapy 84/121 (69%) CA within 90 days of therapy 65/119 (55%) New Kit GEP Sample 91/91 (100%) GEP 70 High Risk 40/91 (44%) GEP 5 High Risk 39/91 (43%) GEP CD-1 subgroup 5/91 (5%) GEP CD-2 subgroup 17/91 (19%) GEP HY subgroup 14/91 (15%) GEP LB subgroup 6/91 (7%) GEP MF subgroup 9/91 (10%) GEP MS subgroup 9/91 (10%) GEP PR subgroup 31/91 (34%) GEP proliferation index >= 10 28/91 (31%) GEP centrosome index >= 3 26/91 (29%) n/N (%): n- Number with factor, N- Number with valid data for factor ND: No valid observations for factor Figure 1A Figure 1A. Figure 1B Figure 1B. Figure 1C: OS by GEP5 Figure 1C:. OS by GEP5 Disclosures Zangari: Norvartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Research Funding; Millennium: Research Funding. van Rhee:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Morgan:Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Myeloma UK: Membership on an entity's Board of Directors or advisory committees; International Myeloma Foundation: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Membership on an entity's Board of Directors or advisory committees; MMRF: Membership on an entity's Board of Directors or advisory committees.
Databáze: OpenAIRE
Externí odkaz: