Publication Date:
2015-12-03
Description:
Background: The well-described prognostic impact of tumor characteristics and biology in multiple myeloma (MM), such as the combination of cytogenetics, the International Staging System (ISS) and lactate dehydrogenase (LDH, Moreau et. al., JCO, 2014) as well as frailty (Palumbo et al., Blood, 2015) significantly influence patient outcomes. However, only limited data on the impact of infections during therapy exist (Rajkumar et al., Lancet Oncology, 2010). Therefore, we hypothesized that severe infections during induction therapy (IT) in transplant-eligible MM influence dosage of therapies, treatment responses after IT and survival. Patients and Methods: From 05/2005 until 05/2008, 399 patients were randomly assigned to receive IT with either three cycles of VAD (vincristine, VIN, i.v. 0.4mg, days 1-4; doxorubicine, DOXO, i.v. 9mg/m2, days 1-4; dexamethasone, DEX, p.o. 40mg, days 1-4, 9-12, 17-20; n=201, arm A) or PAD (bortezomib, BTZ, i.v. 1.3mg/m2, days 1, 4, 8, 11; DOXO i.v. 9mg/m2, days 1-4; DEX p.o. 40mg, days 1-4, 9-12, 17-20; n=194, arm B), followed by high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) and either thalidomide (arm A) or bortezomib (arm B) maintenance within the German part of the joint GMMG-HD4/HOVON65 trial (Sonneveld et al., JCO, 2012). After exclusion of ineligible patients, 395 patients (99.0%) were evaluable for analyses. Any severe infection (equal or greater grade 3, according to the Common Terminology Criteria for Adverse Events, Version 4.0) during IT (at least once, defined from first until last date of application of IT medication) occurred in 105 patients (VAD n=53/198 and PAD n=52/192, 26.9% of all patients, missing data n=5). Results: Among patients with a severe infection during IT in the VAD and PAD arms, total DEX and DOXO doses (equal dosage in VAD/PAD group) were significantly lower (median DEX dose (mg/m2): 689.0 [77.7, 1014.1] vs. 742.3 [0.0, 1324.1], p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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