How to Manage Patients with Lenalidomide-Refractory Multiple Myeloma.

Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient's first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated.

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.

Subcutaneous bortezomib in newly diagnosed patients with multiple myeloma nontransplant eligible: Retrospective evaluation.

Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ~13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery, improves tolerability without impairment of efficacy. The aim of this study was to evaluate the safety and effectiveness of SQ bortezomib-based combinations in nontransplant eligible patients with newly diagnosed myeloma in a real-world setting. A total of 135 patients (median age [range] = 76 [58-89], International Staging System-III = 54%, median follow-up = 14.8 months [1-40], Intensive group [twice weekly bortezomib] = 65%, Optimized group [weekly bortezomib] = 35%) were included and evaluable for safety, whereas 121 were evaluable for effectiveness. Overall response rate (95% CI) was 61% (53%, 71%) (complete response = 27%, very good partial response = 13%, and partial response = 21%) and median progression-free survival was 22.2 months (95% CI: 16.1-not reached). The 3-year overall survival was 75%. The most frequent grade 3-4 adverse events were thrombocytopenia (18%), neutropenia (17%), and anemia (11%). Peripheral neuropathy of any grade was observed in 44% of patients (2% with grade 3). Comparison between regimens (Intensive vs Optimized) showed similar overall response rate (57% vs 70%) and PFS (25 vs 19 months). A similar safety profile was observed between regimens. Thus, SQ bortezomib showed similar effectiveness and better tolerability as compared with results from intravenous bortezomib studies, and showing no differences either in effectiveness or safety in different bortezomib-based combinations.

Cambra system in patients awaiting hematopoietic progenitor cell transplant and high caries risk.

BACKGROUND: Recent times have witnessed a significant increase in the number of patients affected by problems related to oncological treatment Aims of this study is to evaluate dental affectation among patients awaiting hematopoietic progenitor cell transplant (HPCT), and they showed high caries risk, so it should establish a protocol prior to transplantation. MATERIAL AND METHODS: The study included 72 patients due for HPCT. Clinical and radiological explorations were performed and oral photos taken. The amount of caries, missing teeth and fillings were registered for each patient. CAO, DMFS and Restoration Indices were calculated. RESULTS: 83% of patients presented caries. 48 patients (67%) had lost at least one tooth. Only 32 patients (44%) had received some sort of conservative treatment. The average CAO index value obtained was 10.37. The DMFS index showed an average of 27.06 affected surfaces. Of the 72 patients studied, 40 (56%) showed a restoration index value of zero. CONCLUSIONS: These patients presented a high number of carious teeth and a low restoration index. The presence of so many possible septic foci in an individual, who will later become susceptible to infection, highlights the importance of preventative treatment and bucco-dental restoration within this patient population. These patients with a high caries risk can be treated with CAMBRA system. Key words:Hematopoietic progenitor cell transplantation, high caries risk, state of oral health, haematological disease, CAMBRA system.

Influence of oral health on mucositis in patients undergoing hematopoietic progenitor cell transplantation (HPCT)

Aims: To establish whether or not the state of patient oral health can influence the occurrence and/or severity of oral mucositis during hematopoietic progenitor cell transplantation (HPCT).Materials and Methods: The study included 72 patients awaiting HPCT. Prior to transplantation, clinical exploration and radiology were carried out and oral photographs were taken. This evaluated the extent of caries present, the number of missing teeth and the number of dental fillings in each patient; CAO (Caries and Obturations Index)DMFS (Decayed, Missing, and Filled Surfaces) and Restoration Indices were calculated. Gingival pathology was also examined by means of the Ainamo and Bay Gingival Bleeding Index. O’Leary’s Plaque Index was used to evaluate the level of patient oral hygiene. This data was analyzed to see if it exercised any influence on the mucositis grade suffered during HPCT. Results: 96,87% of patients suffered some degree of mucositis during their treatment by the Transplant Unit. The grade of mucositis was seen to be influenced by the number of missing teeth (ANOVA p<0.016) and by the DMFS Index (ANOVA p< 0.038). Although this was not one of the aims of this study, patient age and the administration of colony-stimulating factors were also seen to influence these clinical manifestations. Conclusions: The state of prior oral health can influence decisively the mucositis suffered during transplantation (AU)

Influence of oral health on mucositis in patients undergoing hematopoietic progenitor cell transplantation (HPCT).

AIMS: To establish whether or not the state of patient oral health can influence the occurrence and/or severity of oral mucositis during hematopoietic progenitor cell transplantation (HPCT). MATERIALS AND METHODS: The study included 72 patients awaiting HPCT. Prior to transplantation, clinical exploration and radiology were carried out and oral photographs were taken. This evaluated the extent of caries present, the number of missing teeth and the number of dental fillings in each patient; CAO (Caries and Obturations Index) DMFS (Decayed, Missing, and Filled Surfaces) and Restoration Indices were calculated. Gingival pathology was also examined by means of the Ainamo and Bay Gingival Bleeding Index. O'Leary's Plaque Index was used to evaluate the level of patient oral hygiene. This data was analyzed to see if it exercised any influence on the mucositis grade suffered during HPCT. RESULTS: 96,87% of patients suffered some degree of mucositis during their treatment by the Transplant Unit. The grade of mucositis was seen to be influenced by the number of missing teeth (ANOVA p<0.016) and by the DMFS Index (ANOVA p< 0.038). Although this was not one of the aims of this study, patient age and the administration of colony-stimulating factors were also seen to influence these clinical manifestations. CONCLUSIONS: The state of prior oral health can influence decisively the mucositis suffered during transplantation.