Rob Miani joined the MMRF team as Chief Financial Officer in 2016. Most recently he was the Vice President of Finance and Corporate Controller of Aptuit, LLC, a global contract research organization providing integrated early discovery to mid-phase drug development services in the pharmaceutical industry. Rob has over 20 years of leadership experience in the private and public sectors, holding managerial positions in the renewable energy, private equity, Internet and technology industries, including Davenport Newberry, Oak Investment Partners and INT Media Group. He began his career with Arthur Anderson LLP in the Assurance and Business Advisory Services Division. Rob is a CPA and received his BS degree in Accounting from Fairfield University.
ASH 2020 Day 2 – Relapsed/Refractory Multiple Myeloma
Sunday’s myeloma session at ASH brings us information on many treatment combinations using standard myeloma agents—some that are available today and one hopefully available soon—for patients with relapsed or refractory disease. This session brought us updates on:
- The anti-CD38 monoclonal antibodies – Darzalex (daratumumab) and Sarclisa (isatuximab)
- Melflufen
Relapsed/Refractory Multiple Myeloma
Darzalex and Sarclisa Combinations
Darzalex has been combined with Velcade, Revlimid, and Kyprolis and is approved for use with these agents for patients with relapsed or refractory myeloma. And now, with the availability of the subcutaneous (subq) – injection – formulation of Darzalex that is, Darzalex Faspro, European investigators used the subq version in a phase 3 trial comparing Darzalex Faspro-Pomalyst-dexamethasone (dex) with Pomalyst-dex (ABSTRACT 412).
In this trial, 304 patients who had received one or more prior lines of therapy were evenly divided between the 2 groups (Pomalyst-dex with or without Darzalex Faspro). The results showed:
- Darzalex Faspro-Pomalyst-dex significantly reduced the risk of progression or death by 37% versus Pomalyst-dex alone (progression-free survival 12.4 months vs 6.9 months).
- Darzalex Faspro-Pomalyst-dex prolonged time to disease progression in patients who were refractory to Revlimid (9.9 months vs 6.5 months)
- Responses with the triplet combination were deeper than the doublet: >6 times higher complete response rate or better (25% vs 4%) and >4 times higher minimal residual disease (MRD) negativity rate (9% vs 2%)
- Frequency of infusion reactions was low, and the duration of drug administration was short—making this regimen very convenient for patients.
This combination regimen may soon be added to the growing list of approved uses of Darzalex in the relapsed or refractory setting!
The combination of Darzalex-Cytoxan-dexamethasone with or without the addition of Pomalyst was studied by Canadian investigators in order to determine if this would be a useful regimen for patients who are no longer responsive to Revlimid—a challenging patient population to treat (ABSTRACT 413).
In a phase 2 trial, 120 relapsed or refractory patients—who had received at least one prior line of therapy and 95% were refractory to Revlimid—were divided into 2 groups:
- Arm A: Darzalex-Cytoxan-Pomalyst-dex
- Arm B: Darzalex-Cytoxan-dex and then Pomalyst only added at the time of disease progression
In this study, the IV formulation of Darzalex was used. The results showed:
- 88.6% of patients responded in Arm A vs 50.8% in Arm B
- Time before disease progressed was not reached for patients in Arm A and 8.8 months in Arm B
Sarclisa—the other anti-CD38 monoclonal antibody—was approved earlier this year in combination with Pomalyst-dex for patients with relapsed or refractory myeloma. Sarclisa continues to be studied in other combinations such as with Kyprolis-dex.
Today’s presentation by Dr. Tom Martin at the University of California, San Francisco reviewed data from the phase 3 trial comparing Sarclisa-Kyprolis-dex with Kyprolis-dex (ABSTRACT 414). Over 300 patients were divided between the 2 treatment groups (Kyprolis-dex with or without Sarclisa). The results showed:
- 72.6% of patients achieved a very good partial response or better with Sarclisa vs 56.1% without.
- Minimal residual disease (MRD) negativity was achieved in 30% of patients receiving Sarclisa vs 13% without.
- Longer time until disease progression was seen in the patients who received Sarclisa-Kyprolis-dex and in both MRD-negative and MRD-positive patients
Melflufen
Melflufen is an investigational agent that targets certain enzymes in the myeloma cell which releases chemotherapy (ie, melphalan, the same drug most commonly used prior to a stem cell transplant) into the cell, killing it.
Melflufen has been studied previously in the HORIZON trial in combination with dex with 29% of patients responding. Most of these patients were heavily pretreated and refractory to Pomalyst or Darzalex. In today’s presentation, melflufen-dex was combined with Darzalex or Velcade (ABSTRACT 417). Patients received either of the following treatments:
- Darzalex Arm: Darzalex-melflufen-dex
- Velcade Arm: Velcade- melflufen-dex
The results showed that adding Darzalex or Velcade to melflufen-dex has encouraging activity in a heavily pretreated patient population. We look forward to seeing more mature data as the trial progresses!
The FDA granted priority review to melflufen based on the data from the phase 2 HORIZON study where it was used in combination with dexamethasone. It is hoped that approval will be for the treatment of myeloma patients who are triple-class refractory myeloma. The review could happen as soon as the first quarter of 2021!
That’s all for today! Check back tomorrow for the last of the myeloma sessions at ASH…
