KD-PACE chemotherapy regimen as a salvage therapy for aggressive, refractory multiple myeloma

Novel therapies for multiple myeloma.

Combination Therapy with Bortezomib or Carfilzomib and Selinexor Induces Nuclear Localization of Ikbα and Overcomes Acquired Proteasome Inhibitor Resistance in Human Multiple Myeloma

Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients. We report a case of 40-year-old man with immunoglobulin D (IgD) multiple myeloma whose disease was refractory to at least 5 different chemotherapy regimens including proteasome inhibitors and immunomodulatory drugs. The clinical studies assessing daratumumab did not include any patients with IgD myeloma which is a rare form of multiple myeloma and to our knowledge is the first study reporting use of daratumumab in IgD myeloma.

Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients

Effective use of panobinostat in combination with other active agents in myeloma in a novel five-drug combination: Case report and interesting observations.

High-Dose Melphalan and Granulocyte-Macrophage Colony-Stimulating Factor for Refractory Multiple Myeloma

Thalidomide Therapy and Deep Venous Thrombosis in Multiple Myeloma

Bispecific CS1-BCMA CAR-T Cells Are Clinically Active in Relapsed or Refractory Multiple Myeloma: An Updated Clinical Study

The first in class proteasome inhibitor bortezomib (B) received its initial regulatory approval for therapy of patients with multiple myeloma (MM) in the relapsed/refractory setting. Modulation of proteasome function, however, is also a rational strategy for chemosensitization, and a variety of agents have shown synergistic activity with bortezomib pre-clinically, including anthracyclines. This formed the basis for evaluation of a regimen of bortezomib with pegylated liposomal doxorubicin (PLD). PLD+B, in a phase I study, induced a predictable and manageable toxicity profile, and showed encouraging anti-MM activity. In a recent international, randomized phase III trial, PLD+B demonstrated a superior overall response rate and response quality compared to bortezomib alone, as well as a longer time to progression, duration of response, progression-free survival, and overall survival. Sub-analyses revealed benefits in almost all clinically relevant subgroups, including several which would be considered to have high-risk disease. These findings have led to the establishment of the PLD+B regimen as one of the standards of care for patients with relapsed and/or refractory myeloma. Efforts are now underway to build on this combination further by adding other active anti-myeloma agents. In this review, we will discuss the role of PLD+B as an important addition to our therapeutic armamentarium for patients with MM.

Lenalidomide with Low or Intermediate Dose Dexamethasone in Patients with Relapsed or Refractory Myeloma

Daratumumab in Combination with Dexamethasone in Resistant or Refractory Multiple Myeloma: Primary Results of the IFM2014-04 Trial

Real -World Outcomes for Relapsed or Refractory Multiple Myeloma Patients Treated with Lenalidomide and Daratumumab Sparing Triplet Regimens: A United States Retrospective Cohort Study

Alkaline Phosphatase (ALP) Variation During Carfilzomib Treatment Is Associated to Best Response in Multiple Myeloma.

7620 Background: Thalidomide is an active single agent in advanced relapsed or refractory multiple myeloma (MM). Combination of low dose thalidomide with bendamustine and prednisolone might be a way to maintain efficacy of the drug without dose limiting toxicity (DLT). Methods: The treatment consists of a fixed dose of bendamustine (60mg/qm) day 1, 8, and 15 and prednisolone (100 mg) day 1, 8, 15, and 22. At the same time, thalidomide was given in patients cohorts with escalating doses, starting with 50 mg to a maximum of 200 mg daily. 8 patients (4 after conventional chemotherapy and 4 after APBSCT) were enrolled at each dose level. Cycles were repeated every 28 days for a minimum of 2 and a maximum of 10 cycles until a maximal response was achieved, a DLT or a disease progression were observed. 23 patients ( 8 in the first dose level with 50 mg thalidomide, 8 in the second dose level with 100 mg and 7 patients in the third dose level with 200 mg) are enrolled until now. The number of prior treatment regimens was 2 or more in all patients. 6 patients were refractory for the last treatment. Median age was 67 years (range: 40 - 78). Results: All patients completed 2 cycles of BPT-treatment and were hence evaluable. Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR). 20 of 23 patients responded after at least 2 cycles of chemotherapy with 3 CR, 5 VGPR, 11 PR and 2 MR. 2 patients had stable disease. With a median follow up of ten months, EFS and OS at twelfe months were 36 % and 85 %, respectively. Most common site effects were constipation (10 patients WHO grade 1, 8 patients WHO grade 2), polyneuropathy (14 patients WHO grade 1, 2 patients WHO grade 2) and somnolence (4 patients WHO grade 1). None of the 23 patients developed dose-limiting hematoxicity as defined by an ANC < 1,0 Gpt/l for > 7 days or an ANC < 0,5 Gpt/l for > 3 days or platelet count < 25 Gpt/l. Short neutropenia was reported in 8 patients (WHO grade 3 and 4) but no thrombocytopenia was observed. Conclusions: BPT with a dose between 50 and 200 mg thalidomide daily is well tolerated in patients with relapsed or refractory MM. No significant financial relationships to disclose.

A Phase 1b Study of Step-up Dosing with ABBV-383, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed or Refractory Multiple Myeloma