OncoAlert

The phase 3 LITESPARK-005 trial evaluated patient-reported outcomes (PROs) for belzutifan, a HIF-2α inhibitor, versus everolimus in patients with advanced renal cell carcinoma previously treated with immune checkpoint and anti-angiogenic therapy. 

Oncology Here & Now

In this interview, OncoAlert faculty members Dr. Joseph McCollom from Parkview Health (USA) and Dr. Cristiane Bergerot from OncoClinicas (Brazil) explore supportive care and the future of telemedicine. Their discussion spans the evolution of telehealth—from its pivotal role during the pandemic to its current applications—and what lies ahead.

Join us for this insightful conversation!

Dr. Misty Shields guides us through this great paper out on Cancer (ACS) on the TOP advances in Small Cell Lung Cancer. Small cell lung cancer (SCLC) remains a leading cause of cancer mortality, with its aggressive nature and frequent relapse leading to poor outcomes. In recent years, immunotherapy has provided some survival benefits, and in 2024, key breakthroughs have significantly improved patient outcomes. Notable advances include the use of consolidative durvalumab immunotherapy for limited-stage SCLC, new insights into timing immunotherapy with radiation, and promising treatments such as the bispecific T-cell engager tarlatamab and antibody-drug conjugates. Precision medicine approaches, like neuroendocrine subtyping, may guide future treatments, while advocacy efforts, such as the Small Cell SMASHERS group @SCLCSMASHERS
 , offer new support for patients with this historically stigmatized disease.

​Misty Dawn Shields MD PhD (Presenter and first author) Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA

Oncology Here & Now

In this interview, Dr. Elisa Agostinetto from the Jules Bordet Institute in Belgium speaks with Dr. Maryam Lustberg from Yale Cancer Center. Together, they dive deep into the use of CDK 4/6 inhibitors in the adjuvant treatment of breast cancer. Their discussion covers the use of Abemaciclib and Ribociclib following the monarchE and NATALEE trials, applications in the treatment of male breast cancer, and much more.

Join us!

In this interview with Dr. Silke Gillessen & Dr. Aurelius Omlin , we delve into the origins, Topics and evolution of the Advanced #ProstateCancer Consensus Conference

@APCCC_Lugano

  began in 2015 to address critical questions in prostate cancer management where evidence is lacking or conflicting. Over the years, the conference has focused on various evolving topics, such as oligometastatic disease, treatment sequencing, and new imaging technologies.

 The 2024 APCCC highlighted major discussions on next-generation imaging, genomic biomarkers, and diagnostic challenges, with a strong emphasis on the need to balance cutting-edge technology with clinical practicality.

 Looking ahead to APCCC 2026, the event will continue to address key issues, including the risk of overtreatment, international disparities in imaging access, and the integration of comorbidities into treatment decision-making. With a welcoming atmosphere, APCCC invites healthcare professionals worldwide to engage in these important discussions and contribute to shaping the future of prostate cancer care.

In newly diagnosed multiple myeloma (NDMM), recent studies highlight the critical role of minimal residual disease (MRD) in guiding treatment decisions and improving outcomes. A significant trial showed that adding isatuximab (Isa) to lenalidomide, bortezomib, and dexamethasone (RVd) increased MRD negativity rates after induction therapy compared to RVd alone. MRD negativity was achieved in 50% of patients receiving Isa-RVd versus 36% in those receiving RVd. Additionally, Isa-RVd provided longer progression-free survival (PFS) in MRD-positive patients, though PFS was similar between Isa-RVd and RVd in MRD-negative patients. This suggests Isa offers a significant advantage for MRD-positive patients.

After a median follow-up of 48 months, patients achieving MRD negativity after induction or transplant had significantly better PFS compared to those who remained MRD-positive. The GMMG-HD7 trial, the first phase 3 study to confirm the long-term benefits of achieving MRD negativity with an 18-week induction regimen, demonstrated that deep MRD responses can result in lasting benefits, even without post-transplant consolidation therapy. Future analyses will assess the role of maintenance therapy with or without isatuximab.

Another study examined MRD progression (MRD-P) in NDMM patients treated with quadruplet therapy and autologous stem cell transplantation (ASCT). Though rare, MRD-P predicted imminent progression to full disease. Patients with MRD-P had shorter time to progression and poor survival free from failure of second-line therapy. MRD-P was driven by a plasma cell population resistant to existing therapies, including monoclonal antibodies, highlighting the need for new markers and treatment strategies for high-risk patients.

The CEPHEUS phase 3 trial evaluated the addition of daratumumab (DARA) to the standard VRd regimen in NDMM patients who were transplant-ineligible or deferred transplant. The D-VRd combination significantly increased MRD negativity rates at both the 10^-5 and 10^-6 sensitivity thresholds and led to sustained MRD negativity in more patients than VRd alone. This deeper response resulted in superior PFS, with over 80% of MRD-negative patients remaining progression-free at 54 months. D-VRd improved outcomes in both MRD-positive and MRD-negative patients, positioning it as a new standard of care for transplant-ineligible or deferred patients.

A final study explored whether sustained MRD negativity could allow for discontinuation of lenalidomide maintenance after ASCT. Patients who achieved sustained MRD negativity after three years of lenalidomide maintenance discontinued therapy, with MRD testing every six months. Of the 194 patients, 26.3% achieved sustained MRD negativity, with most remaining MRD-negative for up to 30 months post-therapy. Only 23% became MRD-positive, and a small number progressed to active disease. Among those who restarted lenalidomide, the median time to progression was 9.5 months. This suggests sustained MRD negativity may serve as a marker for safely discontinuing lenalidomide, though further trials are needed to confirm these findings.

In conclusion, MRD status plays a vital role in optimizing treatment and improving outcomes in NDMM. From the benefits of isatuximab and daratumumab in enhancing MRD negativity to the possibility of safely discontinuing maintenance therapy, MRD testing is proving essential in multiple myeloma management.

Disclosure: Supported by Sanofi.

Welcome to this OncoAlert Session Round Up during ASH24, focusing on Multiple Myeloma pharmacologic therapies.

GMMG-HD7 Trial (JCO Publication)
This phase 3 trial evaluated adding isatuximab (Isa) to the standard RVd (lenalidomide, bortezomib, dexamethasone) regimen in transplant-eligible patients with newly diagnosed multiple myeloma. Part 1 randomized 662 patients to Isa-RVd or RVd, followed by autologous stem cell transplantation and a second randomization to lenalidomide or Isa-lenalidomide maintenance. Isa-RVd showed higher minimal residual disease (MRD) negativity rates post-transplant (66% vs 48%) and improved progression-free survival (PFS) with a hazard ratio of 0.70 (P = .0184). Isa-RVd plus lenalidomide maintenance further improved PFS (P = .016), underscoring Isa’s role in prolonging MRD negativity and PFS.

IMROZ Trial (Phase 3)
This trial analyzed Isa-VRd (isatuximab, bortezomib, lenalidomide, dexamethasone) versus VRd in transplant-ineligible patients with newly diagnosed multiple myeloma. Isa-VRd led to significant improvements in PFS and deeper, sustained MRD negativity, with 68.6% achieving MRD negativity by month 36 compared to 50.8% in the VRd group. Isa-VRd also resulted in lower MRD loss rates during maintenance and improved conversion from MRD positivity to negativity, leading to longer PFS. These findings highlight Isa-VRd’s potential for faster, durable responses and support its use to improve long-term outcomes in these patients.

UK MRA Myeloma XI+ Trial
The phase 3 UKMRA/NCRI Myeloma XI+ trial compared KRdc (carfilzomib, lenalidomide, dexamethasone, cyclophosphamide) to sequential triplet therapies (CRd, CTd) in newly diagnosed multiple myeloma patients. After a median follow-up of 102 months, KRdc improved PFS (56 vs 37 months, hazard ratio 0.69, P < 0.001) across cytogenetic risk groups, with higher MRD negativity rates. Early MRD negativity correlated with better PFS. While overall survival was similar in contemporaneously randomized patients (76% vs 71% at 60 months), non-contemporaneous controls showed an overall survival benefit with KRdc (76% vs 68%, hazard ratio 0.80, P = 0.011). These results emphasize the depth of responses with KRdc, particularly for high-risk patients, and the importance of early MRD negativity for improved PFS and survival.

DREAMM-7 Trial (Phase 3)
This trial compared belantamab mafodotin (BVd) versus daratumumab (DVd), both combined with bortezomib and dexamethasone, in relapsed/refractory multiple myeloma. BVd demonstrated a significant PFS benefit (36.6 vs 13.4 months, hazard ratio 0.41, P < 0.00001), with higher complete response and MRD negativity rates (25% vs 10%). BVd also showed a longer response duration (35.6 vs 17.8 months) and early trends favoring overall survival (84% vs 73% at 18 months). Median overall survival was not reached, but projections estimate 84 months for BVd versus 51 months for DVd. BVd's safety profile included manageable ocular events, positioning it as a promising option for relapsed/refractory multiple myeloma after first relapse.

AQUILA Trial (NEJM Publication)
This phase 3 trial evaluated subcutaneous daratumumab as monotherapy versus active monitoring in high-risk smoldering multiple myeloma. Among 390 patients, daratumumab reduced the risk of progression or death by 51% compared to monitoring (hazard ratio 0.49, P < 0.001) after a median follow-up of 65.2 months. At five years, PFS was 63.1% in the daratumumab group versus 40.8% in the monitoring group. Overall survival was higher with daratumumab (93.0% vs 86.9%). Daratumumab was well-tolerated, with hypertension being the most common grade 3 or 4 adverse event (5.7%), and no new safety concerns emerged. Daratumumab significantly delayed progression to active multiple myeloma and improved survival in high-risk patients.

Disclosure: Supported by Sanofi.

A great Pleasure to Present the first Advanced Prostate Cancer Consensus Conference #APCCC24 Webinar/Podcast on Management of patients with Advanced #ProstateCancer : Cases from #APCCC24

LINK TO ARTICLE
https://sciencedirect.com/science/article/pii/S0302283824026101

The  @OncoAlert Round Up Covering July 26-Aug 1, 2024   

REGISTER at http://Oncoalert360.com or https://oncoalert.m-pages.com/nhMpwe/oncoalert-newsletter-registration

Discussing
Shield Blood test FDAApproved for #ColorectalCancer Screening
https://ascopost.com/news/july-2024/guardant-health-s-shield-blood-test-approved-by-the-fda-as-a-primary-screening-option-for-colorectal-cancer/

INSIGHT Trial in #NSCLC
https://thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00270-5/abstract

Combining PSMA-PETand PROMISE in #ProstateCancer
https://sciencedirect.com/science/article/pii/S1470204524003267

Review in RCC #KidneyCancer 

@b_szabados

@drfrankiejs

@tompowles1

 
https://thelancet.com/journals/lancet/article/PIIS0140-6736(24)00917-6/abstract

Immune & Gene Expressionin ER Low & Neg #BreastCancer by 

@vitti10

 
https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djae178/7724836?searchresult=1&login=false

Top Advances of the year: #Immunotherapy & #EndometrialCancer 

@BanerjeeSusana

@PelegHasson

 
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35417

ASCOGuidelines on cannabis in Adults Cancer
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35461?af=R

Welcome to this Hematology Round Up from #EHA24
WE have focused on on Hematologic malignancies with abstracts presented on June 15nd, 2024

The first presentation was abstract s100
This Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ) .
Presented by Dr. Facon
This trial presentation had a concomitant publication on the @NEJM
at #ASCO24 last week
https://lnkd.in/d2dRh6Hp



The Second presentation was abstract S101

THE LANDSCAPE OF TP53 MUTATIONS AND THEIR PROGNOSTIC IMPACT IN CHRONIC LYMPHOCYTIC LEUKEMIA

https://lnkd.in/dYg6DqPT

The Next presentation was abstract S102

FIRST RESULTS OF THE APOLLO TRIAL: A RANDOMIZED PHASE III STUDY TO COMPARE ATO COMBINED WITH ATRA VERSUS STANDARD AIDA REGIMEN FOR PATIENTS WITH NEWLY DIAGNOSED, HIGH-RISK ACUTE PROMYELOCYTIC LEUKEMIA


https://lnkd.in/d2ZM6Z4Q

The Next presentation is abstract S103

ASCIMINIB (ASC) PROVIDES SUPERIOR EFFICACY AND EXCELLENT SAFETY AND TOLERABILITY VS TYROSINE KINASE INHIBITORS (TKI) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML) IN THE PIVOTAL ASC4FIRST STUDY


https://lnkd.in/dxiets8m

Our final Presentation is Late breaking abstract 3438

GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (GLOFIT-GEMOX) FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): RESULTS OF A GLOBAL RANDOMIZED PHASE III TRIAL (STARGLO)

https://lnkd.in/dMWxnyF4

Thank you for your attention and enjoy #EHA24

Disclosure: This Hematology Round Up was supported by Sanofi