The American Society of Hematology meeting is the largest meeting of experts in the world for blood cancers. How any patient or patient advocate can sort through the mountain of data presented at these meetings is next to impossible? How do we uncover the “best of the best abstracts” on myeloma care and treatment? I asked some of the world’s best myeloma specialists what they considered to be their favorites from ASH 2017. I am so pleased to provide this summary of the “Best of the Best ASH 2017 Myeloma Abstracts” to the myeloma patient community. A few points of note are 1) BCMA is an excellent target for CAR T and monoclonal antibodies 2) Daratumumab has been tested in combination with many drugs and “Things always go better with DARA!” 3) Early treatment of myeloma improves Overall Survival. and 4) For Relapsed/Refractory Multiple Myeloma Patients new drugs are in the pipeline like Selinexor, Venetoclax, and Melflufen with much improved efficacy than existing drugs.
These doctors all have presented at ASH and all attended this year’s meeting. I thank you for your long standing outreach to the myeloma patient community. We find that your efforts are extremely valuable to helping myeloma patients to become more knowledgeable and become our own best advocates. These outstanding doctors in alphabetical order:
C. Ola Landgren, MD – Memorial Sloan-Kettering Cancer Center, New York, NY
Gareth Morgan, M.D., Ph.D – University of Arkansas for Medical Sciences, Little Rock, AR
Paul G Richardson, MD – Dana Farber Cancer Institute, Boston Mass.
Vincent Rajkumar, MD – Mayo Clinic, Rochester, MN
Saad Usmani, MD – Levine Cancer Institute, Charlotte, NC
Dr. Ola Landgren’s Favorite Myeloma Abstracts
1. Abstract 435 – Minimal residual disease in multiple myeloma: Final analysis of the IFM 2009 trial.
This large randomized study for newly diagnosed multiple myeloma confirms that sequencing based MRD is more sensitive than flowcytometry (can rule out 1 tumor cell in 1 million cells versus 1 in 100,000), and that sequencing based MRD negativity has the same PFS independent of therapy (i.e. with versus without transplant). This study is clinically very important.
CLICK HERE for a Myeloma Crowd post on this abstract.
2. Abstract 510 – Daratumumab monotherapy for patients with intermediate or high risk smoldering multiple myeloma: Centaurus, a randomized, open label multicenter phase 2 study.
An important randomized study showing that daratumumab is well tolerated in smoldering myeloma and it leads to significantly longer PFS. This study has already triggered a phase 3 trial of daratumumab in highrisk smoldering myeloma. Based on these preliminary results, I think the phase 3 will make daratumumab the first FDA approved drug for smoldering myeloma. Stay tuned!
CLICK HERE for a Myeloma Crowd post on this abstract.
3. Abstract 3133 – MRD Response-Driven Phase I/II Study for Newly Diagnosed Multiple Myeloma Patients Using Higher Doses of Twice-Weekly Carfilzomib (45 and 56 mg/m2) in Combination with Lenalidomide and Dexamethasone
This is an innovative study for newly diagnosed multiple myeloma patients that uses MRD status to determine the duration of combination therapy. Current treatment paradigm is to give every myeloma patient the same number of cycles. Here, patients who become MRD negative fast get fewer cycles, and patients who are slower to reach MRD negativity will receive more cycles.
4. Abstract 332 – Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies (SPMs) in multiple myeloma patients.
An increasingly important topic for myeloma drug development will be to consider longterm benefits and risks. As patients live longer and longer it will be very important to avoid unnecessary risks. This study evaluates longterm risks of transplant. With an increased range of treatment options and assays to determine MRD negativity this is very timely.
5. Abstract 741 – Deep and durable responses in patients with relapse/refractory myeloma treated with GSK2857916, an antibody drug conjugate against B-cell maturation antigen (BCMA): preliminary results from part 2 of study BMA117159
BCMA is an evolving target for the treatment of myeloma. Five ongoing CAR T cell trials target BCMA. Also, BCMA-targeted BiTE antibodies (CD3) are in development Here, a BCMA-targeted monoclonal antibody with a conjugated toxin shows 60% ORR in a monotherapy setting. This is very interesting and will be important to follow with regard to depth and duration of responses.
CLICK HERE for a Myeloma Crowd post on this abstract.
Dr. Garath Morgan’s Favorite Myeloma Abstracts
1. Abstract 60 – Identification of Novel Oncogenes and Tumor Suppressor Genes in Newly Diagnosed Multiple Myeloma (Brian Walker)
This abstract is identifying the genes that drive the process of myeloma will play an important role in developing clinical approaches that treat specific pathways and biologically relevant pathways so as to develop both new treatments and new ways of evaluating those treatments.”
CLICK HERE for a Myeloma Crowd post on this abstract.
2. Abstract 265 – Crowdsourcing a High-Risk Classifier for Multiple Myeloma Patients (Andrew Dervan at Celgene)
Dr. Morgan states, “Crowdsourcing can lever an unknown quantity of highly relevant experience to address significant clinical questions. In this case high risk disease will benefit from investigators addressing whether it can be recognised when patients first present to the clinic.”
CLICK HERE for a Myeloma Crowd post on this abstract.
3) Abstract 396 – The Mutational Landscape of Relapse in High Risk Myeloma is Significantly Impacted by the Depth of Response but not Maintenance Lenalidomide (John Jones ICR UK)
This abstract shows evidence that lenalidomide maintenance does not affect the number of mutations or evolutionary pathways to relapse but the depth of response is a key determinant.
Dr. Paul G Richardson’s Favorite Myeloma Abstracts
1) Abstract 740 – Durable Clinical Responses in Heavily Pretreated Patients with Relapsed/Refractory Multiple Myeloma: Updated Results from a Multicenter Study of bb2121 Anti-Bcma CAR T Cell Therapy
Dr. Richardson states, “This CAR T cell therapy shows remarkable results including an Overall Response Rate (ORR) of 94%. With a median follow-up of 40 weeks the rate of Complete Response (CR) is 54%, and high MRD(Minimal Residual Disease) negative rate, with generally manageable toxicity. Brilliant Results!”
CLICK HERE for a Myeloma Crowd post on this abstract.
2) Abstract 741 – Deep and durable responses in patients with relapse/refractory myeloma treated with GSK2857916, an antibody drug conjugate against B-cell maturation antigen (BCMA): preliminary results from part 2 of study BMA117159
This Phase II data is new and shows 60% response rate – a major new finding. This OSS is at levels never before recorded in the RRMM group. A response rate twice that of single agent Daratumumab.
CLICK HERE for a Myeloma Crowd post on this abstract.
3) Abstract 3135 – Selinexor in Combination with Weekly Low Dose Bortezomib and Dexamethasone (SVd) Induces a High Response Rate with Durable Responses in Patients with Refractory Multiple Myeloma (MM)
Dr. Richardson states, In Relapsed Refractory Multiple Myeloma – Selinexor in combination with Bortezomib and Dexamethasone (SVT) has better tolerability and impressive activity in heavily pretreated relapsed refractory multiple myeloma patients.”
CLICK HERE for a Myeloma Crowd post on this abstract.
4) Abstract LBA-4 – Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)
This trial shows striking benefit to adding DARA to a standard combo – recognizing that VMP is not usually given in the USA but is a very important platform outside of the USA in non- transplant eligible MM patients.
5) Abstract 3150 – First Report on Overall Survival (OS) and Improved Progression Free Survival (PFS) in a Completed Phase 2a Study of Melflufen in Advanced Relapsed Refractory Multiple Myeloma (RRMM)
In RRMM patients, the combination of Melflufen/dex has shown remarkable ORR of 40% in RRMM patietns as well as PFS and OS in two large phase 2 studies shown after novel therapies have failed. Melflufen may stop multiple myeloma growth by binding to and damaging the DNA in cancer cells. Once inside the cell, it is converted to melphalan, a drug already used to treat multiple myeloma.
Dr. Vincent Rajkumar’s Favorite Myeloma Abstracts
1) Abstract 903 – Tackling Early Morbidity and Mortality in Myeloma (TEAMM): Assessing the Benefit of Antibiotic Prophylaxis and Its Effect on Healthcare Associated Infections in 977 Patients
Dr. Rajkumar states, “Here’s why this abstract is important: Early deaths now with effective therapy for MM are mainly due to infections. #1 Drayson et al show that prophylactic levofloxacin can save lives.”
CLICK HERE for a Myeloma Crowd post on this abstract.
2) Abstract 510 – Daratumumab Monotherapy for Patients with Intermediate or High-Risk Smoldering Multiple Myeloma (SMM): Centaurus, a Randomized, Open-Label, Multicenter Phase 2 Study
Dr. Craig Hofmeister et al Daratumumab phase 2 trial provides critical data for upcoming Dara Phase III trials in SMM. Early available data is encouraging.
CLICK HERE for a Myeloma Crowd post on this abstract.
3) Abstract 402 – Curative Strategy for High-Risk Smoldering Myeloma (GEM-CESAR): Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT, Consolidation with Krd and Maintenance with Rd
Dr. Mateos Cesar trial tests the hypothesis that myeloma can be cured if treated early with the most effective drugs. Along with upcoming ASCENT trial in USA, it’s part of a long term plan of strategic phase 2 trials to determine curability of myeloma. The intent is not to change practice.
4) Abstract LBA-4 – Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)
Dr. Rajkumar states, “Dr. Mateos et al gives first Phase III data of Dara in frontline setting. Wish there was a 3rd arm without Dara maintenance. Still important data and will sync with many other monoclonal antibody frontline RCTs.”
5) Abstract 741 – Deep and Durable Responses in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (MM) Treated with Monotherapy GSK2857916, an Antibody Drug Conjugate Against B-Cell Maturation Antigen (BCMA): Preliminary results from Part 2 of Study BMA117159
Dr. Rajkumar states, “This Phase II data is new and shows 60% response rate – a major new finding. Trudel Anti BCMA is exciting. Single agent activity in RRMM.”
CLICK HERE for a Myeloma Crowd post on this abstract.
Dr. Saad Usmani’s Favorite Myeloma Abstracts
1) Abstract 3110 – Daratumumab (DARA) in Combination with Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Patients with Newly Diagnosed Multiple Myeloma (MMY1001): Updated Results from an Open-Label, Phase 1b Study
Dr. Usmani states “I have chosen this abstract because of the favorable safety data, the primary end-point of this small phase I, as it sets up the stage for larger Phase II/III trial designs to build on the Kyprolix/Revlimid/dex experience generated by Drs. Landgren and Jakubowiak. This study lines up well with other presentations that have combined Dara with front line regimens (such as Dara-VMP, Mateos et al; Dara-RVd, Voorhees PV et al). We still have to wait for more data before preferentially assigning one regimen over the other based on disease biology/risk at diagnosis.”
CLICK HERE for a Myeloma Crowd post on this abstract.
2) Abstract 1879 – Interim Safety Analysis of a Phase 2 Randomized Study of Daratumumab (Dara), Lenalidomide (R), Bortezomib (V), and Dexamethasone (d; Dara‐Rvd) Vs. Rvd in Patients with Newly Diagnosed Multiple Myeloma Eligible for High‐Dose Therapy and Autologous Stem Cell Transplantation.
Dr. Usmani states “I have chosen this abstract because it is clinically very relevant to the current standard of care practice in the US, also asks the question whether or not we can put more patients in MRD negativity by introducing Dara in to the standard of care schema.”
CLICK HERE for a Myeloma Crowd post on this abstract.
3) Abstract LBA-4 – Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)
This trial shows striking benefit to adding DARA to a standard combo – recognizing that VMP is not usually given in the USA but is a very important platform outside of the USA in non- transplant eligible MM patients.
The future for myeloma patients looks bright based on all these outstanding abstracts highlighted by these remarkable myeloma specialists. Good luck and may God Bless your cancer journey. For more information on multiple myeloma survival rates and treatments CLICK HERE and you can follow me on twitter at: https://twitter.com/grpetersen1
