Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).
We evaluated the occurrence of severe infections in 192 consecutive adult recipients of volunteer unrelated donor allogeneic hematopoietic stem cell transplants, with a detailed analysis of severe infections after receipt of cord blood transplants (CBTs; n = 48) or bone marrow transplants (BMTs)/peripheral blood stem cell transplants (PBSCTs; n = 144). At a 3-year median follow-up, CBT recipients had a higher risk of developing any severe infection (85% versus 69% in BMT/PBSCT recipients, P < .01). CBT recipients had a higher incidence of severe bacterial infections before day +100, but at 3 years the risks of these and other infections were similar in the CBT and BMT/PBSCT groups. In addition, the 100-day and 3-year incidences of infection-related mortality (IRM) did not differ between groups (P = .2 and .5, respectively). In multivariate analysis, the most significant risk factor for IRM in all 192 patients was monocytopenia (.2 x 10(9)/L). In CBT recipients, only neutropenia (.2 x 10(9)/L) on day +30 and low nucleated cell dose infusion (< 2 x 10(7)/kg) showed a trend for increased IRM (P = .05 in both cases). Stem cell source had no effect on day +100 or 3-year nonrelapse mortality (NRM), cytomegalovirus infection, cytomegalovirus disease (7% versus 6%), or overall survival (36% versus 39%, respectively). The number of mismatches in HLA (A, B, and DRB1) had no effect on any outcome in CBT recipients. In contrast, in the BMT/PBSCT group, the presence of any mismatch by low or high-resolution HLA typing (A, B, C, and DRB1) increased NRM and decreased overall survival (P < .01). IRM was the primary or secondary cause of death in 61% and 59% of CBT and BMT/PBSCT recipients who died, respectively. Our results confirm the relevance of severe infectious complications as source of severe morbidity and NRM after volunteer unrelated donor hematopoietic stem cell transplantation in adults, but suggest that CBT recipients have a similar risk of dying from an infection if an accurate selection of a cord blood unit is done.
Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235. (Blood. 2012;120(13): 2581-2588)
IntroductionMultiple myeloma (MM) is the second most frequent hematologic malignancy and it usually affects elderly patients. Melphalan and prednisone (MP) has been the standard of care in the past for this patient population, resulting in complete response (CR) rates ranging from 2% to 5% with median overall survival (OS) from 2 to 3 years. [1][2][3] The introduction of novel agents thalidomide (Thal), bortezomib (V), and lenalidomide (R) for the treatment of elderly MM patients has significantly increased the CR rate, and this translated into prolonged time to progression (TTP), progression-free survival (PFS), and OS. Therefore, the concept of "the longer the duration of the response the longer the survival" used for most hematologic malignancies would also be applicable to MM and particularly to elderly patients because (usually) two-thirds of the survival duration in the elderly population derives from the efficacy of the first line of therapy. Accordingly, an attractive current challenge is to explore the capacity of novel agents, such as thalidomide, bortezomib, and lenalidomide to maintain the high response rate achieved upfront with these drug combinations. 4 Concerning Thal, 6 randomized trials have compared MP and Thal (MPT) with MP, 5-10 and in 3 of them Thal was also used as maintenance therapy until disease progression. 5,8,9 Maintenance induced an improvement in both overall response rate (ORR; upgrade ranging from 17% up to 30%) and PFS (prolongation ranging from 2 up to 7 months) but with only marginal benefit for OS. An Austrian trial has compared the value of Thal plus interferon maintenance versus interferon alone in elderly patients who had received inductio...
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