Recent Advances in the Treatment of Patients with Multiple Myeloma.

In the past 20 years, few diseases have seen as great progress in their treatment as multiple myeloma. With the approval of many new drugs and the limited availability of clinical trials comparing head-to-head the different possible combinations, the choice of the best treatments at each stage of the disease becomes complex as well as crucial since multiple myeloma remains incurable. This article presents a general description of the novelties of the whole treatment of multiple myeloma, from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses, including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research, and that will surely play a relevant role in the treatment of this devastating disease in the coming years.

The safety of daratumumab for the treatment of multiple myeloma.

INTRODUCTION: The overall survival of patients with multiple myeloma (MM) has changed dramatically in the last decade. MM remains an incurable plasma cell disorder but immunotherapy with monoclonal antibodies (MoAbs) has emerged as a promising treatment. Areas covered: Fully published, clinical trials including patients with relapsed or refractory MM were reviewed. Safety data of daratumumab (DARA) single-agent or in combination regimens have been addressed. Additionally, infusion-related reactions, data on special populations, and DARA-interference with laboratory testing, including assessment of MM response in patients have also been addressed. Expert opinion: Daratumumab both as single agent and in combination regimens has shown a favorable safety profile without significant increase in toxicities. Extensive clinical development of DARA is currently ongoing and given the efficacy that has been seen with this drug in clinical trials, DARA is likely to change the landscape of myeloma treatment.

Which therapies will move to the front line for multiple myeloma?

INTRODUCTION: Despite substantial progress, multiple myeloma (MM) remains an incurable disease. Recently the availability of several novel drugs with different and innovative mechanisms of action (daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat) has increased the therapeutic options but has also increased complexity in the management of patients with MM. Areas covered: The outstanding results observed in the relapsed setting with regimens including these new drugs has provided the investigators with several treatment options that are being tested also in patients with newly diagnosed MM. Fully published phase 2 and randomized, phase 3 trials including new drugs in patients with relapsed and/or refractory MM have been reviewed. In addition, the progressive incorporation of these new drugs in the front-line treatment of MM and the potential impact of these new therapies in the management of patients with newly diagnosed MM has also been addressed. Expert commentary: In the near future, several novel anti-MM drugs will move from the relapsed to the front-line setting. While the increasing range of effective therapeutic agents is very encouraging it adds to the complexity of treatment decisions and prospective trials are needed to help clinicians to determine which could be the best therapeutic approaches for the different subgroups of patients with newly diagnosed MM.

Infectious complications in patients with newly diagnosed multiple myeloma: A complication from the past?

Infectious complications are an important risk factor for early mortality in patients with multiple myeloma. However, data about the impact and severity of infections in these patients in the era of new therapies have not been properly analyzed. This review has reviewed the incidence and severity of infections complications and infection-related mortality during induction treatment in patients with newly diagnosed myeloma receiving regimens with new drugs within randomized trials. The results show that infections are still a major cause of morbidity, especially among elderly patients receiving immunomodulatory drugs seen in up to 28% of patients in some trials vs less than 10% among transplant-eligible patients. Overall infection-related mortality ranged from 0-7% in transplant-ineligible patients, with no infection-related deaths in the majority of the trials including younger patients. Strategies directed to further reduce these complications and a better knowledge of their impact in patients treated outside clinical trials are needed.

Clinical treatment of newly diagnosed multiple myeloma.

The introduction of the novel agents, thalidomide, bortezomib and lenalidomide as part of the frontline induction both in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients' prognosis. Current treatment goals are aimed to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their quality of life. This article reviews the current landscape of frontline treatment both in transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma.

Front-line lenalidomide therapy in patients with newly diagnosed multiple myeloma.

The availability of novel drugs with different and innovative mechanisms of action such as proteasome inhibitors such as bortezomib and immunomdulatory agents as thalidomide and lenalidomide have changed the landscape of the treatment of patients with newly diagnosed multiple myeloma, allowing the development of several new therapeutic regimens both for transplant-eligible and -ineligible patients. Among these new agents, lenalidomide has become one of the most commonly used in these patients. In this article, we review the current state-of-the-art of different induction and maintenance lenalidomide-containing regimens administered in transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma. We also discuss the safety profile and potential long-term side effects of this drug and analyze its utility in certain subgroups of patients like those with high-risk disease or different degrees of renal impairment.