ASH Abstracts 2019

Today, the American Society of Hematology (ASH) released late-breaking abstracts (https://ash.confex.com/ash/2019/webprogram/Session17468.html) in advance of the 2019 ASH Annual Meeting, Dec. 7-10 in Orlando, Florida. 

According to ASH, the six late-breaking abstracts are “the Program Committee's selections of the highest-impact abstracts, featuring substantive, novel, and groundbreaking data that were not available by the general abstract submission deadline and would otherwise not be presented at the ASH annual meeting.”

Among them is an important study (https://ash.confex.com/ash/2019/webprogram/Paper132629.html), the CANDOR trial, which compared carfilzomib (Kyprolis®), dexamethasone, and daratumumab (Darzalex®) (KdD) to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma patients, and showed the added benefit of daratumumab.

The primary endpoint in this study was progression-free survival (PFS). Median PFS was “not reached” for KdD versus 15.8 months for Kd, a highly significant benefit. Benefit was sustained in multiple subgroups, including patients refractory to lenalidomide (Revlimid), and, significantly, more and deeper (MRD-negative) responses occurred with KdD. Overall, KdD is an excellent therapy in this patient population and had a favorable benefit-risk profile, which was very promising.

My ASH 2019 Preview blog (https://www.myeloma.org/cure-blog/ash-top-10-2019-immune-therapies-again-dominate-news) focused on the most important myeloma oral presentations. But in addition to those are several hundred ASH 2019 posters. Among them, several themes emerge:

Role of cytogenetic abnormalities:

• 1q+: Abstract #2193 (https://ash.confex.com/ash/2019/webprogram/Paper125407.html) (Chromosome 1q Amplification Is Associated with a History of Prior Malignancies Among Patients Newly Diagnosed with Multiple Myeloma) and abstract #4343 (1q21 Gain May Challenge the Role of t(4;14) As an Adverse Prognostic Marker of Multiple Myeloma)
• t(11;14): Abstract #3066 (https://ash.confex.com/ash/2019/webprogram/Paper126867.html) (Outcomes of Patients with t(11;14) Multiple Myeloma: An International Myeloma Working Group Multicenter Study) and abstract #4580 (https://ash.confex.com/ash/2019/webprogram/Paper129880.html) (Role of High-Dose Melphalan and Autologous Stem Cell Transplantation in Multiple Myeloma Patients Presenting with t(11;14))

Importance of imaging

• PET/CT combined with MRD testing: Abstract #3170 (https://ash.confex.com/ash/2019/webprogram/Paper125062.html) (Precision Medicine Based on the Achievement of Sustained Undetectable Minimal Residual Disease (MRD) By Next-Generation Flow (NGF) and Imaging Leads to Significant Reduction in Risk of Progression of Patients with Multiple Myeloma (MM)) (https://ash.confex.com/ash/2019/webprogram/Paper125062.html) and abstract #4321 (https://ash.confex.com/ash/2019/webprogram/Paper125134.html) (MRD Evaluation By PET/CT According to Deauville Criteria Combined with Multiparameter Flow Cytometry in Newly Diagnosed Transplant Eligible Multiple Myeloma (MM) Patients Enrolled in the Phase II Randomized Forte Trial)

Confirmation of the importance of MRD testing

• Abstract #4322 (https://ash.confex.com/ash/2019/webprogram/Paper124645.html): Forte trial results (Minimal Residual Disease Evaluation By Multiparameter Flow Cytometry and Next Generation Sequencing in the Forte Trial for Newly Diagnosed Multiple Myeloma Patients)
• Abstract #4742 (https://ash.confex.com/ash/2019/webprogram/Paper124191.html): Meta-analysis findings (Expanded Meta-Analyses Confirms the Association between MRD and Long-Term Survival Outcomes in Multiple Myeloma (MM))

Potential role of mass spectrometry testing

• Abstract #581 (https://ash.confex.com/ash/2019/webprogram/Paper127717.html) (Qip-Mass Spectrometry in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment): MRD and QiP mass spectrometry in the CESAR trial 
• Abstract #3090 (https://ash.confex.com/ash/2019/webprogram/Paper129760.html) (A Longitudinal Evaluation of Euroflow and Combined Quantitative Immunoprecipitation (QIP) and Free Light Chain (FLC) Mass Spectrometry (MS) in Functional High Risk Multiple Myeloma); abstract #4375 (https://ash.confex.com/ash/2019/webprogram/Paper128175.html) (Quantitative Immunoprecipitation Free Light Chain Mass Spectrometry (QIP-FLC-MS) Simplifies Monoclonal Protein Assessment and Provides Added Clinical Value in Systemic AL Amyloidosis): (https://ash.confex.com/ash/2019/webprogram/Paper128175.html) Both studies evaluate the role of mass spectrometry in amyloidosis.
• Abstract #4377 (https://ash.confex.com/ash/2019/webprogram/Paper128938.html)(MALDI-TOF Mass Spectrometry in Serum for the Follow-up of Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Combination Therapy); abstract #4386 (https://ash.confex.com/ash/2019/webprogram/Paper130771.html) (Prognostic Implications of Serum Monoclonal Protein Positivity By Mass-Fix in Bone Marrow Minimal Residual Disease Negative (MRD-) Patients with Multiple Myeloma): (https://ash.confex.com/ash/2019/webprogram/Paper130771.html) Both studies evaluate the role of mass spectrometry in disease monitoring.

In addition, many individual treatment trial results will be reported at ASH. Two may be of particular interest:

• Abstract #1888 (https://ash.confex.com/ash/2019/webprogram/Paper126015.html) (Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma): The follow-up of the venetoclax Bellini trial results
• Abstract #3154 (https://ash.confex.com/ash/2019/webprogram/Paper127608.html) (Efficacy and Safety of CAR-T Therapy with Safety Switch Targeting Bcma for Patients with Relapsed/Refractory Multiple Myeloma in a Phase 1 Clinical Study): Results with a CAR T trial from Shanghai, China using CAR T cells with a “safety switch.”

There is little doubt that the 2019 ASH will be exciting and interesting. These few abstracts I have highlighted are certainly among those not to be missed. 
For additional analyses of 2019 ASH research presentations from the IMF, please tune in to these two programs:

• "Making Sense of Treatment," the International Myeloma Working Group (IMWG) Live Stream Conference Series, Dec. 9, 8:30 – 9:30 pm ET. I will be joined by Dr. Joseph Mikhael (IMF Chief Medical Officer) and Dr. María-Victoria Mateos to tackle questions facing myeloma doctors and patients in light of study results presented at ASH. Available online (https://www.myeloma.org/videos/imwg-conference-series-ash-2019-orlando-fl), both live and archived.  
• The Living Well teleconference “The Best of ASH 2019: What Patients and Caregivers Need to Know,” Jan. 9, 7:00 pm ET. This IMF teleconference (https://www.myeloma.org/videos/best-ash-2019) summarizes research findings from the annual meeting for myeloma patients and caregivers.
   

Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.