Our Magnificent Myeloma Motivation

Just as those limits will bring my group chair tenure to an end next March, term limits also mean that this summer the long-time chair of our Barlogie-Salmon Myeloma Committee, Dr. Robert Orlowski, will step down from his role.

Dr. Orlowski has been one of our most effective leaders for quite some time. In addition to being a gifted researcher, he has been an inspirational champion of myeloma research and a transformational mentor to many. 

He has also served as a trusted advisor and even  the conscience of our Board of Governors, always speaking up on the need to strictly and fairly maintain the democratic process within our group. Although he’ll remain a member of our myeloma committee (and our publications and immunotherapeutics committees), I’ll miss his calm voice and cool reasoning in our group leadership meetings.

Under Dr. Orlowski’s hand, the myeloma committee has launched, completed, or published (in some cases, all three) a number of important trials that have advanced the treatment of myeloma and related diseases.

Most prominently, it completed and published S0777, a randomized phase III study that added bortezomib, a proteosome inhibitor, to a standard lenalidomide plus dexamethasone combination in patients newly diagnosed with multiple myeloma. That investigational combination (VRd) significantly improved both progression-free survival and overall survival, and S0777 established the triplet as standard of care for these patients. 

These results prompted the National Comprehensive Cancer Network to upgrade the VRd regimen to a category one recommendation for both transplant-eligible and transplant-ineligible patients with symptomatic myeloma.

Also based on the S0777 results (and on the products of an 18-month intensive audit and review of S0777 data), in 2019 the European Medical Association’s (EMA’s) Committee for Medical Products for Human Use approved VRd as therapy for patients with myeloma who are not eligible for stem cell transplant.

Not only did Dr. Orlowski lead the first clinical study of bortezomib in advanced hematologic malignancies (some years before becoming our committee chair), he has also studied the ubiquitin-proteasome pathway as a target in myeloma therapy for much of his career. It’s an area of research that was pioneered by his father (for details, see this history of multiple myeloma that appeared in the ASH 50th Anniversary Review issue of the journal Blood).

During his tenure as chair, the committee launched, completed and reported on several other significant studies:

• S1211, the first randomized study completed in high-risk multiple myeloma. It built on the VRd combination from S0777, and its results support a role for continued maintenance therapy in patients with high-risk disease.
• S1304, which compared low-dose versus high-dose carfilzomib with dexamethasone in patients with relapsed or refractory myeloma. The trial found no benefit for the higher dose over the standard treatment.
• S1702, which found isatuximab, already approved for myeloma, demonstrated efficacy in treating relapsed or refractory AL amyloidosis.

The committee’s S1803, which closed to accrual earlier this year, is comparing lenalidomide plus daratumumab to lenalidomide alone as post-transplant maintenance therapy for patients with myeloma. And S2209, which opened in 2023 and continues to enroll, is a randomized phase III in patients newly diagnosed with myeloma who aren’t candidates for transplant.

As chair, Dr. Orlowski established working groups for AL amyloidosis and Waldenström’s macroglobulinemia, and the committee has opened trials in both of these rare diseases. In AL amyloidosis, in addition to S1702 detailed above, the committee more recently launched S2213, a randomized phase III study.

And in 2021 it opened S2005, a phase II study comparing venetoclax and rituximab to ibrutinib and rituximab for patients with previously untreated Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma. Cross-group collaboration and coordination have been a hallmark of Dr. Orlowski’s strategy for our myeloma research, and S2005 was developed in collaboration with ECOG-ACRIN.

Happily, Dr. Orlowski will continue to make valuable contributions to SWOG’s work, and as his tenure as myeloma chair draws to a close, we have a search underway for a worthy successor. 

Please note our SWOG research committee chairs provide strategic direction in their research area, contribute to SWOG’s overall strategic planning, and participate regularly in management of the group. A chair’s committee-specific activities include overseeing protocol development, mentoring early career investigators, monitoring ongoing trials, and analyzing and reporting results, among other roles.

The full position posting for chair of the Barlogie-Salmon Myeloma Committee is online. If you know – or are – the ideal candidate, please reach out. Candidates should send a CV or NIH biosketch with a one-page vision statement to lesliew@ohsu.edu by June 25, 2025.

Dr. Orlowski is entirely at home in the pantheon of illustrious myeloma research leaders in SWOG, with his immediate predecessors in that role, Drs. Bart Barlogie and Sydney Salmon. I cannot thank him enough for his outstanding service to SWOG and our patients.

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Trial of the Week

S2101: Biomarker-Stratified CaboZantinib and NivOlumab (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants with Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study

Activation of Stage II: May 2025

Well, this is not the first Trial of the Week appearance for S2101, the pilot study for our immunoMATCH precision medicine trial. But it is the first appearance for S2101’s second stage, which has just recently opened.

S2101 (aka, the BiCaZO study) is a phase II study using a cabozantinib and nivolumab combination to treat patients with advanced melanoma or head and neck squamous cell carcinoma (HNSCC) whose disease has progressed after anti-PD1 therapies.

Stage I of the study closed to accrual late last summer for interim analysis, after the enrollment of 54 participants. 

Stage II opened with the activation of protocol revision #5 on May 1st.

In Stage I, the trial finalized the molecular tests used to assign iMATCH patients to treatment groups. These tests assess tumor-mutation burden (TMB) and use gene expression profiling (GEP) to assign a tumor inflammation score (TIS). Screened patients were stratified based on those biomarker results, although those results did not affect their registration to the treatment step.

In Stage II, however, once biomarker results are in, screened patients will be registered for treatment on the trial only if a slot is available in the appropriate biomarker cohort.

In evaluating the feasibility of using iMATCH’s biomarker testing for patient stratification, Stage II’s metric is the proportion of trial participants who have their biomarker results returned in 21 days or less.

Study chairs for the trial are:

• Siwen Hu-Lieskovan, MD, PhD, of the University of Utah Huntsman Cancer Institute,
• Paul Swiecicki, MD, of the University of Michigan,
  and
• Katerina Politi, PhD, of the Yale Cancer Center.

The trial is now open at almost 200 sites nationwide. 

Although 17 institutions enrolled to the study in Stage I, just two institutions together accounted for almost one-half of all patients accrued – the University of Michigan’s Rogel Cancer Center and the Huntsman Cancer Institute at the University of Utah (with impressive showings by the Mayo Clinic and the Virginia Commonwealth University’s Massey Cancer Center as well).

Stage II offers a fresh chance for other institutions to climb the leaderboard!

Learn more on the SWOG S2101 page or the CTSU S2101 page. A patient-friendly summary of the study is also available, in both English and Spanish, as an aid in presenting the trial to your patients.