ESH MM 2018 | How to treat newly diagnosed multiple myeloma

The 4^th International Conference on Multiple Myeloma, organized by the European School of Haematology (ESH), took place on 5–7 of October 2018 in Mandelieu, France. Unlike other meetings that mainly aim to disseminate new research findings and updates from clinical trials, the purpose of this particular conference, was to educate health care professionals on a variety of topics related to multiple myeloma (MM), which were delivered by world-leading experts. In addition to a session dedicated to the biology, diagnosis, and management of smoldering multiple myeloma (SMM), there were also talks covering the diagnosis and management of other plasma cell dyscrasias, including primary plasma cell leukemia (PCL) and POEMS syndrome.

This article outlines key highlights on the two sessions about treatment of newly diagnosed (ND) MM patients.

Thierry Facon from the University Hospital of Lille, France, chaired the session on frontline therapy in patients not eligible for autologous stem cell transplant (ASCT). 

Alessandra Larocca from the University of Turin, Italy, discussed that although the age limit for an ASCT is currently being expanded to over 65 years of age, there are no clear guidelines on how to treat elderly patients, especially frail patients. It is advisable that elderly patients complete the IMWG Frailty Score to evaluate their performance status and assist in adjusting treatment to their physical needs. Treatment modifications to be considered include the use of alkylator-free regimens, doublets rather than triplets and lowering the drug dose.

Sonja Zweegman from VU University Medical Center in Amsterdam, the Netherlands, described the European guidelines applied to this patient group. The two possible options in Europe include bortezomib/melphalan/prednisone (VMP) and lenalidomide/dexamethasone (Rd). Sonja Zweegman noted that at present, there is no need to compare these treatments but it is important to understand how to choose between these two regimens. There are two main criteria to use when deciding which regimen to opt for. The first is the characteristics of the disease; a study that compared the results of the GIMEMA-MM0305 trial with those of the European Myeloma Network-01 (EMN-01) trial showed that VMP is more effective than Rd in a subgroup of patients with high-risk MM. The second criterion is the patient’s preferences; some patients may prefer Rd because it is administered orally but others may prefer VMP because it offers longer intervals between treatment administration.

Noopur Raje from the Massachusetts General Hospital in Boston, US, talked about the approved available options for this group of patients in the US, which include lenalidomide/bortezomib/dexamethasone (RVd), carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/cyclophosphamide/dexamethasone (VCd). In addition, although VMP is not commonly used in NDMM ineligible for ASCT in the US, daratumumab in combination with VMP has recently been approved for the treatment of these patients. A key point raised was that although most data about treatment options are obtained from clinical trials, older patients are underrepresented in these trials.

We interviewed Kwee Yong from University College London Hospitals in London, UK, who discussed ongoing trials for this group of patients when new drugs are not available.

Michele Cavo from S.Orsola's University Hospital in Bologna, Italy, chaired the session on frontline therapy of patients eligible for ASCT and talked about the European versus (vs) the US guidelines for these patients. He highlighted that although in Europe the standard of care for NDMM patients, who are fit and younger than 65 years of age, is induction therapy followed by an ASCT, in the US this is not always the case. While for patients with high-risk MM an ASCT is offered immediately, for those with low-risk MM an ASCT may be delayed.

Philippe Moreau from the University Hospital of Nantes, France, discussed the different induction therapies available for this patient group. These should control the disease fast, achieve a high response, result in minimal toxicity, and allow adequate stem cell harvest. Currently, there is a very limited number of phase III trials that may allow deciding on the best drug combination and the optimal number of induction cycles. The triplet combination bortezomib/cyclophosphamide/dexamethasone (VCd) revealed a non-inferior superiority and lower toxicity profile in comparison to bortezomib/doxorubicin/dexamethasone (PAd) [MM5 trial  of the German-Speaking Myeloma Multicenter Group (GMMG)].

An ongoing phase III trial compares the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) with that of bortezomib/lenalidomide/dexamethasone (VRd) as induction treatments. At the moment, there are no available data about a possible superiority of KRd compared to VRd. 

There are several ongoing clinical trials that are examining the efficacy of quadruplets as induction treatments for NDMM patients eligible for ASCT:

• The GMMG-HD6 phase III trial compares elotuzumab (E) in combination with bortezomib/lenalidomide/dexamethasone (E-VRd) vs VRd
• The DSMM XVII a phase III trial compares elotuzumab (E) in combination with carfilzomib/lenalidomide/dexamethasone (E-KRd) vs KRd prior to ASCT
• The Cassiopeia phase III trial compares daratumumab (D) in combination with bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd
• A phase II clinical trial compares daratumumab (D) in combination with lenalidomide/bortezomib/dexamethasone (D-RVd) vs RVd
• The GMMG-HD7 phase III trial compares isatuximab (ISA) in combination with lenalidomide/bortezomib/dexamethasone (ISA-RVd) vs RVd

Finally, we interviewed Annemiek Broijl from the Erasmus Medical Centre in Rotterdam, the Netherlands, who addressed the topic of treatment of high-risk NDMM patients and highlighted the need for clinical trials that will provide a clear association between minimal residual disease (MRD)-negativity and cure.