Autotransplants in older multiple myeloma patients: hype or hope in the era of novel agents?

Engelhardt, Monika; Ihorst, Gabriele; Caers, Jo; Günther, Andreas; Wäsch, Ralph

doi:10.3324/haematol.2016.154807

Cited by 10 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expert panel emphasizes that current clinical research should maintain a balance between treatment efficacy and quality of life, identify the optimal sequencing of treatment, the appropriate tools for patient selection, evaluate costs of prolonged novel-agent application versus transplant remission efficacy, and treatment-free intervals, and it should identify how to best induce long-term remission. 110 In the future, objective, prospective and proficiently performed fitness tools may prove to be of benefit before intensive treatment is start ed, especially since fitness assessments made by patients and physicians are not as objective as fitness evaluations derived from well-defined tests and scores. Future randomized studies will also need to evaluate the role of ASCT as salvage treatment in the context of the novel combinations currently available as salvage options.…”

Section: Discussionmentioning

confidence: 99%

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

et al. 2017

Self Cite

View full text Add to dashboard Cite

Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended.

show abstract

Section: Discussionmentioning

confidence: 99%

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“… 35 The application of objective criteria to determine patients’ fitness in the context of co-morbidities should aid optimal selection of both younger and older patients. 36 – 40 …”

Section: Discussionmentioning

confidence: 99%

Melphalan 140 mg/m ² or 200 mg/m ² for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

et al. 2017

View full text Add to dashboard Cite

Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m2 and melphalan 140 mg/m2 are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m2 (n=245) and melphalan 200 mg/m2 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m2 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m2 versus melphalan 140 mg/m2: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m2 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m2 and melphalan 140 mg/m2 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m2 or melphalan 140 mg/m2 for key transplant outcomes (NCT01362972).

show abstract

“…In addition, age, cytogenetics via fluorescence in situ hybridization (FISH after CD138 selection), renal function ( via estimated glomerular filtration rate [eGFR MDRD ]) and lung disease, including lung function tests, were determined as described. 8 – 11 , 22 – 25 We performed interphase FISH on CD138+ plasma cells, which were analyzed using DNA probes specific for the following chromosomal aberrations: t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q32;q23) and t(14;20)(q32;q12 (Abbott Laboratories, IL, USA), XL 5q31/5p12, XCE 9, 11, 15, gain(1q21), del(1p32), del(13q14), del(17p13) and c-myc rearrangements (MetaSystems, Altlussheim, Germany). The score of Wuilleme et al 26 was used to assess ploidy by using gains of at least two of the chromosomes.…”

Section: Methodsmentioning

confidence: 99%

A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

et al. 2017

Self Cite

View full text Add to dashboard Cite

With growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of the analysis herein was to develop and validate an easy to use myeloma risk score (revised Myeloma Comorbidity Index) that allows for risk prediction of overall survival and progression-free survival differences in a large patient cohort. We conducted a comprehensive comorbidity, frailty and disability evaluation in 801 consecutive myeloma patients, including comorbidity risks obtained at diagnosis. The cohort was examined within a training and validation set. Multivariate analysis determined renal, lung and Karnofsky Performance Status impairment, frailty and age as significant risks for overall survival. These were combined in a weighted revised Myeloma Comorbidity Index, allowing for the identification of fit (revised Myeloma Comorbidity Index ≤3 [n=247, 30.8%]), intermediate-fit (revised Myeloma Comorbidity Index 4–6 [n=446, 55.7%]) and frail patients (revised Myeloma Comorbidity Index >6 [n=108, 13.5%]): these subgroups, confirmed via validation analysis, showed median overall survival rates of 10.1, 4.4 and 1.2 years, respectively. The revised Myeloma Comorbidity Index was compared to other commonly used comorbidity indices (Charlson Comorbidity Index, Hematopoietic Cell Transplantation-Specific Comorbidity Index, Kaplan-Feinstein Index): if each were divided in risk groups based on 25% and 75% quartiles, highest hazard ratios, best prediction and Brier scores were achieved with the revised Myeloma Comorbidity Index. The advantages of the revised Myeloma Comorbidity Index include its accurate assessment of patients’ physical conditions and simple clinical applicability. We propose the revised Myeloma Comorbidity Index to be tested with the “reference” International Myeloma Working Group frailty score in multicenter analyses and future clinical trials. The study was registered at the German Clinical Trials Register (DRKS-00003868).

show abstract

Autotransplants in older multiple myeloma patients: hype or hope in the era of novel agents?

Cited by 10 publications

References 18 publications

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

Melphalan 140 mg/m ² or 200 mg/m ² for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

Contact Info

Product

Resources

About

Autotransplants in older multiple myeloma patients: hype or hope in the era of novel agents?

Cited by 10 publications

References 18 publications

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

Melphalan 140 mg/m 2 or 200 mg/m 2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

Contact Info

Product

Resources

About

Melphalan 140 mg/m ² or 200 mg/m ² for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party