How I treat myeloma with new agents

Moreau, Philippe

doi:10.1182/blood-2017-05-743203

Cited by 68 publications

(49 citation statements)

References 47 publications

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“…The next‐generation immunomodulatory drug (IMiD), pomalidomide, and proteasome inhibitors (PIs), carfilzomib and ixazomib, have demonstrated superior potency and toxicity profiles in comparison to the older IMiDs (thalidomide and lenalidomide) and PI (bortezomib) respectively (Lacy et al , ; Siegel et al , ; Kumar et al , ). Also, new classes of drugs, such as the monoclonal antibodies daratumumab (anti‐CD38) and elotuzumab (anti‐SLAMF7) and the histone deacetylase inhibitor panobinostat have been introduced, and several new agents are under investigation (San‐Miguel et al , ; Lokhorst et al , ; Lonial et al , ; Moreau, ).…”

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confidence: 99%

“…Data on the efficacy of retreatment with agents to which patients were previously refractory are scarce. It is mostly advised to consider retreatment with a prior agent only if the patient previously responded and relapsed at least 6 months after the drug was stopped (Nooka et al , ; Harousseau & Attal, ; Moreau, ). Retreatment with first‐line IMiD's and/or PI's could, however, preserve alternative options for later stages of disease and improve cost‐efficacy of treatment.…”

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Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients

et al. 2018

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SummaryThis single‐centre retrospective observational study analysed the efficacy of retreatment with immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) after treatment with daratumumab monotherapy in patients with relapsed and/or refractory multiple myeloma (RRMM). In total 55 patients were treated with daratumumab monotherapy between 2010 and 2017. From this group 29 (53%) IMiD‐refractory patients were retreated with an IMiD after daratumumab and 6 (11%) PI‐refractory patients were retreated with a PI‐based regimen. For the IMiD‐refractory patients the overall response rate (ORR) was 52% (15/29 patients, partial response or better) upon IMiD retreatment, whereas the ORR to PI retreatment was 67% (4/6 patients) in the PI‐refractory group. The immunomodulatory effects of daratumumab may play a role in these high response rates in previously refractory patients. Due to the >6 month‐long persistence of daratumumab in the plasma the subsequent therapies can effectively be considered as combination therapy. Furthermore, the excellent tolerability of daratumumab treatment may enable patients to recover from prior lines of treatment and receive full dosing of subsequent therapies. In conclusion, a high proportion of RRMM patients benefitted from retreatment with IMiDs and PIs after daratumumab treatment. These retreatment options should therefore be explored in RRMM patients progressing on daratumumab monotherapy.

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Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients

et al. 2018

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“…In general, despite progress in the development of effective treatment the disease is still considered incurable (Mateos et al., ). However, there is hope for continuous improvement, especially by introducing promising new agents into the treatment schemes (Moreau, ; Harrouseau & Attal, ).…”

Section: Application To Multiple Myelomamentioning

confidence: 99%

Dynamic prediction: A challenge for biostatisticians, but greatly needed by patients, physicians and the public

et al. 2019

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Prognosis is usually expressed in terms of the probability that a patient will or will not have experienced an event of interest t years after diagnosis of a disease. This quantity, however, is of little informative value for a patient who is still event-free after a number of years. Such a patient would be much more interested in the conditional probability of being event-free in the upcoming years, given that he/she did not experience the event in the s years after diagnosis, called "conditional survival." It is the simplest form of a dynamic prediction and can be dealt with using straightforward extensions of standard time-to-event analyses in clinical cohort studies. For a healthy individual, a related problem with further complications is the so-called "ageconditional probability of developing cancer" in the next t years. Here, the competing risk of dying from other diseases has to be taken into account. For both situations, the hazard function provides the central dynamic concept, which can be further extended in a natural way to build dynamic prediction models that incorporate both baseline and time-dependent characteristics. Such models are able to exploit the most current information accumulating over time in order to accurately predict the further course or development of a disease. In this article, the biostatistical challenges as well as the relevance and importance of dynamic prediction are illustrated using studies of multiple myeloma, a hematologic malignancy with a formerly rather poor prognosis which has improved over the last few years. K E Y W O R D Sage-conditional probability of developing cancer, conditional survival, dynamic prognosis, landmark regression models, time-dependent bias 822In doing so, we consider only absolute CS since this is the quantity of major interest in a clinical context. From a public health or epidemiologic perspective, however, relative CS, defined as the ratio of survival probabilities with the denominator derived from an age-adjusted normal population, may also be a highly relevant quantity (Shack, Braynt, Lockwood, & Ellison, 2013), which is sometimes also used for a statistical definition of cure (Baade, Youlden, & Chambers, 2011).On the other hand, for a healthy individual it might be of interest to know the probability of developing a certain disease, for example, a specific type of cancer. Quantities that are regularly published are age-specific incidence rates. These, however, cannot be directly translated into probabilities since death from other causes, for example, cardiovascular death, constitutes a competing event. Thus, the framework of multistate competing risks models has to be used to account for this fact. In a similar way as argued for CS, the resulting probabilities are of little value for an individual who is still alive and healthy at some age . Here, age-conditional probabilities of developing or dying from cancer are of interest for healthy individuals and today these are frequently reported by tumor registers and/or national statistical offi...

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“…1,2 The natural history of MM was first changed by the introduction of high-dose chemotherapy and ASCT, 3,4 and it was then further improved by the use of novel agents such as the immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide, the proteasome inhibitors (PIs) bortezomib, carfilzomib, and ixazomib, and, most recently, the monoclonal antibodies elotuzumab and daratumumab. 5,6 These therapeutic innovations have led to a significant survival improvement, with the median overall survival (OS) of patients with MM now ranging from 6 to 10 years and depending on the age of the patients at diagnosis. 2,7 Because of the wide availability of new targeted therapies for the treatment of MM, the role of stem cell transplantation (SCT) has been questioned in recent years, with several trials addressing the role and timing of transplantation.…”

Section: Introductionmentioning

confidence: 99%

Is there still a role for stem cell transplantation in multiple myeloma?

Mina

Lonial

2019

Cancer

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High‐dose chemotherapy and autologous stem cell transplantation (ASCT) are a standard of care for transplant‐eligible patients with newly diagnosed multiple myeloma (MM). The introduction of novel agents, which range from immunomodulatory drugs and proteasome inhibitors to monoclonal antibodies and have now been integrated into both induction and salvage regimens, has dramatically revolutionized the treatment landscape of MM and challenged the role of high‐dose chemotherapy and ASCT in treating MM. These advances have led to a number of provocative questions. First, what is the current role of stem cell transplantation (SCT) in comparison with standard‐dose therapy incorporating novel agents? Second, should ASCT be performed upfront (“early”) or later (“delayed”) in the course of the disease? Third, should single or double ASCT be performed? Fourth, is allogeneic SCT still an option for patients with MM? This article provides an overview of available data and evidence‐based responses regarding the role of SCT in MM.

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How I treat myeloma with new agents

Cited by 68 publications

References 47 publications

Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients

Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients

Dynamic prediction: A challenge for biostatisticians, but greatly needed by patients, physicians and the public

Is there still a role for stem cell transplantation in multiple myeloma?

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