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.
The American Society of Clinical Oncology meeting (ASCO) has begun! MMRF will be bringing you all of the latest updates on new research and clinical trials from the meeting. Day 1 began with a number of talks devoted to new therapeutic options for relapsed refractory multiple myeloma (RRMM) patients:
Kd RRMM ARROW study
Dr. Maria Mateos of Spain described a large study of 478 patients that tested Kyprolis-dex in a once per week vs a twice per week regimen. Results included:
- The once weekly group had a higher overall response
- Once weekly dosing improved progression free survival (PFS) by 3.6 months, and reduced risk of progression or death by 30.7%
- No difference in safety was seen between the 2 groups
Overall, this is good news for patients as once weekly dosing of this important myeloma treatment offers a more convenient schedule without loss of effectiveness.
PVd vs Vd RRMM OPTIMISMM study
Dr. Paul Richardson from Dana-Farber, and a member of the MMRC, described a study examining the efficacy of Pomalyst-Velcade-dex vs. Velcade-dex; the study compared PVd (281 patients) vs Vd (278 patients) in RRMM patients with prior Revlimid treatment, including patients who no longer respond to Revlimid (to see if there is any risk of cross-resistance between Revlimid and Pomalyst, which belong to the same class of drugs).
The study showed that:
- PVd reduced risk of progression or death by 39% vs Vd
- PVd showed earlier, deeper, more durable response
- Overall, the results support the use of PVd in first relapse in patients who may no longer respond to Revlimid
D-Kd RRMM MMY1001 study
Dr. Ajai Chari from Mt. Sinai, and a member of the MMRC, presented a study of the combination of Darzalex with Kyprolis-dex. The purpose was to determine safety, drug exposure, and efficacy of Darzalex-Kd in RRMM patients, including Revlimid refractory patients. In this study, Darzalex was administered as single first dose (10 patients) or in a spit first dose (75 patients). They found that
- Darzalex-Kd was efficacious and well tolerated, and led to deep and durable responses regardless of prior Revlimid treatment (including being refractory to Revlimid)
- Split first dose (two 4 hour infusions on consecutive days vs. one 8 hour infusion) was feasible, there was no difference in efficacy, and the split dosing improves convenience
There are currently 2 Phase 3 studies ongoing to test dara-Kd (CANDOR) or dara-Pd (APOLLO) combinations for Revlimid exposed RRMM patients.
PhII VenKd dose escalation (Venetoclax) in RRMM
Dr. Luciano Costa described a study looking at a Venetoclax-Kyprolis-dex combination in 42 patients. Results showed:
- VenKD was tolerable with no safety concerns
- ORR of 80%, response VGPR or better in 57%
- t(11;14) patients has best responses but high risk and standard risk patients had comparable responses
The addition of Kyprolis to Ven-dex, which is targeted therapy for t(11;14) myeloma, was safe and well tolerated. The MMRF supports the continued development of Venetoclax for MM, as it progresses toward FDA approval in the next 1-2 years.
Phase 2 Cord Blood NK cells
The MMRC’s Dr. Nina Shah presented an immunotherapy study looking at the ability of natural killer (NK) cells, a type of T cell, derived from cord blood, to treat myeloma patients. NK cells have been shown to kill myeloma cell lines in the lab. NK cells derived from cord blood are more readily available than CAR-T cells, they are a more “naïve” T cell line meaning they require a less rigorous matching from a donor, and they cause no significant Graft Vs Host Disease or Cytokine Release Syndrome (CRS).
The safety of this therapy was previously demonstrated in a Phase 1 study of 12 patients. The current study followed 33 patients infused with NK cells derived from cord blood followed over 3 years. Results showed that 79% of patients had a VGPR or better, 59% saw 3 year PFS, 61% were MRD negative at day 100.
More work needs to be done before this immunotherapy becomes a viable treatment option.
BCMA CAR-T
The MMRC’s Dr. Noopur Raje presented results from a multicenter Phase 1 trial of the bb2121 BCMA CAR-T therapy. Study CRB-401 enrolled 43 pts, all of which had prior ASCT and were heavily pretreated. The results so far show:
- 63% of patients experienced CRS, but it was mostly low grade and manageable
- Cytopenia was common but reversible by day 32 post infusion
- MRD negative results were achieved in 100% of responding patients (n=16) , median PFS was 17.7 months
- ORR was the same in patients regardless of their level of BCMA expression
- Median duration of response (DOR) for responders was 11 months; patients did experience relapse
The study showed CAR-T is a viable and exciting therapy option that produces rapid and deep responses, but not every patient responds, and patients continue to relapse. There is currently the global KarMMa CAR-T trial ongoing, additional trials in earlier lines of MM are planned, and analysis of predictors of response, toxicity, and progression are ongoing.
To find out more about these and other clinical trials that are currently enrolling patients, visit https://themmrf.org/multiple-myeloma/resources/clinical-trial-finder/ or call one of our Nurse Navigators at 1-866-603-6628.
Check back tomorrow for further updates!
