The appearance of the MoAb represented a revolution in cancer therapy that has already been transferred to MM. In this work the main mechanisms of action of the MoAbs are reviewed, both in their effects on the tumor cell (CDC, ADCC or ADCP), and on the immune system; the clinical data currently available in MM are also reviewed. The first MoAb to be approved for the treatment of MM was elotuzumab, an anti-SLAMF7 MoAb, but in combination with lenalidomide and dexamethasone for patients who had received between 1-3 previous treatment lines because elotuzumab does not work as single agent. Subsequently, the anti-CD38 MoAb daratumumab was approved as monotherapy for the treatment of patients previously exposed to proteasome inhibitors and IMiDs and refractory to the last line, based on the efficacy demonstrated in two studies in highly pretreated and refractory patients, as single agent. More recently, this drug has been evaluated in combination with lenalidomide and dexamethasone and with bortezomib and dexamethasone in randomized trials in which the addition of daratumumab demonstrated a better response rate and progression free survival than the standard without the MoAb, which led to the approval of both combinations for relapsed patients by the FDA. Other anti-CD38 MoAbs, as well as other antibodies directed against the PD1 immune checkpoint, are currently being evaluated, with promising preliminary results. In conclusion, these treatments, which are already available, may increasingly be incorporated into the different therapeutic algorithms, representing a new concept in the treatment of MM.

Daratumumab

Combination therapy

Source

Cite

Citations (0)

Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma

Leukemia (2014)

Meletios Α. Dimopoulos Xavier Leleu Antonio Palumbo Philippe Moreau Michel Delforge

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1–21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment should continue until evidence of disease progression or unacceptable toxicity. Dose-modification schemes have been established for patients who develop neutropenia, thrombocytopaenia and other grade 3–4 adverse events during pomalidomide therapy. Guidance on the prevention and management of infections and venous thromboembolism is provided, based on the available clinical evidence and the experience of panel members. The use of pomalidomide in special populations, such as patients with advanced age, renal impairment or unfavourable cytogenetic features, is also discussed.

Pomalidomide

10.1038/leu.2014.60

Cite

Citations (114)

A172 Peripheral Neuropathy with VMP Resolves in the Majority of Patients and Shows a Rate Plateau

Clinical Lymphoma & Myeloma (2009)

MV Mateos PG Richardson Rudolf Schlag N Khuageva Meletios Α. Dimopoulos

10.1016/s1557-9190(11)70492-9

Cite

Citations (9)

Outcome of first salvage therapy for multiple myeloma (MM) in real-world clinical practice: Results from the third interim analysis of the multinational, observational, non-interventional EMMOS study

Clinical Lymphoma Myeloma & Leukemia (2015)