The virtual 2021 ASCO Annual Meeting (American Society of Clinical Oncology) starts tomorrow, June 4, and runs through June 8. Although it is just not the same without in-person presentations, online discussions of the pending abstracts have been very active. Among the Oral and Poster presentations on myeloma, several stand out as important for current and future decision-making.
As has been the case for the past couple of ASCO, ASH (American Society of Hematology) and EHA (European Hematology Association) meetings, the immune therapy results dominate the headlines. These include both CAR T-cell therapies and bi-specifics. However, there are also key data presented about maintenance with daratumumab in the CASSIOPEIA trial (Dara-VTd: daratumumab + bortezomib + thalidomide + dexamethasone); treatment of high-risk disease in a U.K. trial; the value of selinexor Vd in elderly patients; the occurrence of second primary malignancies after autologous stem-cell transplant; plus the superiority of whole-body MRI (versus PET/CT) in baseline imaging and the emerging role of mass spectrometry from both the STAMINA trial and GEM Spanish trials for low-level disease monitoring.
Many other abstracts provide helpful and interesting information, but I will focus on these highlighted trials.
CAR T-cell therapy
Several abstracts involve Janssen/Legend’s CAR T-cell therapy Cilta-cel, which demonstrates impressive results (abstract 8005) in relapsed and refractory disease with longer follow-up. With a median follow-up of 18 months, the overall response rate is now an impressive 98%, with 80% of patients achieving stringent complete responses, Janssen reported this week. In the new data, 66% of patients were still in remission at 18 months, with an overall survival of 81%. These data are being used to support the application to the FDA, which has been granted priority review status. Cilta-cel results in other disease settings are also presented, with promising results.
Updated results with the bi-specific agent teclistamab (abstract 8007) are also to be presented. This phase II study in patients with heavily pretreated disease will report on 40 patients, of whom 65% achieved a response with acceptable toxicity, Janssen reported this week. Among responders, 58% experienced a VGPR and 30% had a complete response or better. Obviously further follow-up of both efficacy and toxicity are required, especially in light of problems with other bi-specifics currently being evaluated. Results of a trial with the bi-specific elranatamab (abstract 8006) will also be presented, but unfortunately this trial has had to be paused because of serious neurotoxicity.
Daratumumab (dara) maintenance
The longer-term follow-up of the CASSIOPEIA trial (abstract 8004) provides very helpful information about daratumumab maintenance. Among the patients who received the quadruplet (Dara-VTd) for induction and consolidation, the addition of Dara maintenance did not prolong remissions. This has important implications as the use of quadruplets is moving toward more widespread considerations. It seems that if an excellent response has already been achieved there is not added benefit with true maintenance in this particular setting.
Frontline therapy for high-risk disease
In a U.K. study (abstract 8000), newly diagnosed patients received KCd (carfilzomib + cyclophosphamide + dexamethasone) and K maintenance with either KCd or ASCT as consolidation. The result with KCd and ASCT consolidation were equivalent, with high-risk patients continuing to do more poorly overall, indicating a need for alternate strategies for these patients.
Selinexor Vd in elderly patients
In a useful analysis, Thierry Facon and colleagues (abstract 8019) show that patients age 65 years or older gained survival benefit with the well-tolerated selinexor Vd (BOSTON trial) combination, with both improved PFS and overall survival.
Autologous stem-cell transplant (ASCT) and second primary malignancies
In abstract 10507, the longer-term occurrence of second primary cancers (SPMs) is assessed. Of note, 6.62% of patients developed SPMs after receiving ASCT versus 4.87% among those who did not — a significant trend. Obviously, this something to consider in weighing the pros and cons of potential ASCT.
Mass spectrometry testing
Two studies evaluated the role of mass spectrometry testing for serial monitoring of deep responses. In the STAMINA trial (abstract 8009), the mass spectrometry of the blood testing (“MASS-FIX”) provided a convenient and non-invasive method of predicting outcomes equivalent to bone marrow MRD NGF (next-generation flow) testing. Likewise in the GEM trial (abstract 8010), results of bone marrow MRD NGF testing were concordant with the serial mass spectrometry results. In this situation, a complementary role for NGF testing and mass spectrometry evaluation is proposed. Of note, MRD testing is also assessed in another study involving Dara-CVRd, daratumumab + bortezomib + lenalidomide + cyclophosphamide + dexamethasone, (abstract 8001), confirming its utility in patients with ultra-high-risk disease.
Important role of whole-body MRI
In a study from the U.K.’s Institute of Cancer Research (abstract 8012), baseline whole-body MRI (WB MRI) is compared with PET/CT. At least one focal lesion was detected in 50 out of 60 (83.3%) of patients with WB MRI versus 36 out of 60 (60%) by PET/CT, a clear advantage for MRI imaging. There was an even greater advantage related to diffuse disease, in which 81.7% were MRI positive versus 16.7% for PET/CT. Of note, all patients deemed high risk by t[4;14]; t[14;16] del[1q)or del[17p] demonstrated a diffuse pattern with WB MRI. These results definitely substantiate a key role for WB MRI versus the currently recommended PET/CT approaches.
There are numerous interesting abstracts this year. I have highlighted those which I think can become helpful in guiding decision-making and lead to improved patient outcomes. Enjoy the upcoming virtual presentations!
You can watch IMF video interviews with 2021 ASCO researchers and myeloma experts here. Or enter http://bit.ly/imf-asco in your browser!