Association between response kinetics and outcomes in relapsed/refractory multiple myeloma: analysis from TOURMALINE-MM1

© The Author(s) 2018.The association between depth of response in multiple myeloma (MM) and long-term outcomes is well recognized [1,2,3]. Thus, clinicians and patients are often encouraged by a rapid decrease of M-protein when treatment is initiated, and achieving ≥very-good partial response (VGPR) by 4 months of initial diagnosis has been associated with decreased mortality [4]. However, little is known about the association between response kinetics and outcomes. While some reports suggest that early responders may have compromised long-term outcomes compared with late responders [5, 6], these studies were limited, confined to frontline setting only, and based in the era prior to novel-agent availability.TOURMALINE-MM1 was sponsored by Millennium Pharmaceuticals Inc. Writing assistance for this manuscript was provided by Jane Saunders, FireKite (an Ashfield Company, part of UDG Healthcare PLC) and was funded by Millennium Pharmaceuticals Inc

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/ refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches

Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France

Background. Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. Methods. A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. Results. Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). Conclusions. The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies

Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects

Novel calcium phosphate cements containing a mixture of four amino acids, glycine, proline, hydroxyproline and either lysine or arginine (CAL, CAK) were characterized and used for treatment of artificial osteochondral defects in knee. It was hypothesized that an enhanced concentration of extracellular collagen amino acids (in complex mixture), in connection with bone cement in defect sites, would support the healing of osteochondral defects with successful formation of hyaline cartilage and subchondral bone. Calcium phosphate cement mixtures were prepared by in situ reaction in a planetary ball mill at aseptic conditions and characterized. It was verified that about 30–60% of amino acids remained adsorbed on hydroxyapatite particles in cements and the addition of amino acids caused around 60% reduction in compressive strength and refinement of hydroxyapatite particles in their microstructure. The significant over-expression of osteogenic genes after the culture of osteoblasts was demonstrated in the cement extracts containing lysine and compared with other cements. The cement pastes were inserted into artificial osteochondral defects in the medial femoral condyle of pigs and, after 3 months post-surgery, tissues were analyzed macroscopically, histologically, immunohistochemically using MRI and X-ray methods. Analysis clearly showed the excellent healing process of artificial osteochondral defects in pigs after treatment with CAL and CAK cements without any inflammation, as well as formation of subchondral bone and hyaline cartilage morphologically and structurally identical to the original tissues. Good integration of the hyaline neocartilage with the surrounding tissue, as well as perfect interconnection between the neocartilage and new subchondral bone tissue, was demonstrated. Tissues were stable after 12 months’ healing

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches. © 2018, The Author(s)