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Neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for muscle-invasive bladder cancer (January 2022)

For patients with muscle-invasive bladder cancer (MIBC), the optimal regimen for neoadjuvant chemotherapy prior to radical cystectomy is not established. In a phase III trial of almost 500 patients with MIBC treated with either neoadjuvant or adjuvant chemotherapy, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) had similar three-year progression-free survival (PFS) compared with gemcitabine plus cisplatin (GC) [1]. However, among those treated with neoadjuvant chemotherapy, dose-dense MVAC improved three-year PFS over GC (66 versus 56 percent). Although further follow-up is necessary, for most patients with MIBC and good performance status who are receiving neoadjuvant chemotherapy prior to radical cystectomy, we continue to suggest neoadjuvant MVAC regimens over GC.


Nivolumab plus relatlimab in patients with metastatic melanoma (August 2021, Modified January 2022)

For patients with metastatic melanoma, there is interest in combining novel therapies with checkpoint inhibitor immunotherapy to improve outcomes. In a double-blind phase III trial of over 700 patients with treatment-naive advanced melanoma, the addition of relatlimab, a human IgG4 LAG-3-blocking antibody, to nivolumab improved progression-free survival (median 10 versus 5 months), and was well-tolerated [2]. While promising, the combination of nivolumab and relatlimab in this population remains investigational and we continue to suggest nivolumab plus ipilimumab in patients with metastatic melanoma.


Progressive parkinsonism after BCMA-targeted CAR-T cell therapy (January 2022)

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known acute and usually reversible complication of chimeric antigen receptor T (CAR-T) cell therapy, but long-term neurologic effects have not been well documented. A recent case report described the onset of progressive parkinsonism approximately 100 days after administration of ciltacabtagene autoleucel, an investigational CAR-T cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) [3]. Based on postmortem studies, the syndrome appeared to be an on-target effect of CAR-T cells on BCMA-expressing astrocytes and neurons in the basal ganglia. Delayed parkinsonism has also been reported after idacabtagene vicleucel, another BCMA-targeted product. Further studies are needed to understand risk factors and treatment strategies.


Dabrafenib and trametinib in BRAF-mutant NSCLC (January 2022)

The combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has previously shown benefit in BRAF-mutant melanomas, but its role in non-small cell lung cancer (NSCLC) is being evaluated. In a phase II study in 93 patients with advanced NSCLC with the BRAF V600E mutation, the combination of dabrafenib plus trametinib was associated with an objective response rate of 68 percent in previously treated patients and 64 percent in treatment-naive patients [4]. For most patients with advanced NSCLC whose tumors harbor a BRAF V600 mutation, we suggest front-line use of the combination of dabrafenib plus trametinib, rather than chemotherapy and/or immunotherapy.


Routine premedication for PEGylated asparaginase (January 2022)

Asparaginase, a polypeptide of bacterial origin, is an important component of treatment for acute lymphoblastic leukemia, and PEGylated products (eg, pegaspargase, calaspargase) are now preferred for newly diagnosed patients. While they are less immunogenic than nonpegylated E. coli-derived asparaginase, infusion reactions still occur in up to one-third of patients. In 2021, the pegaspargase United States prescribing information was updated to recommend routine premedication with acetaminophen, an H1-receptor blocker, and an H2-receptor blocker administered 30 to 60 minutes prior to each dose [5]. The prescribing information for calaspargase has also been similarly updated [6].


1. Pfister C, Gravis G, Flechon A, et al. Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial. Ann Oncol. 2021;32;5S.


2. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022;386(1):24.


3. Van Oekelen O, Aleman A, Upadhyaya B, et al. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat Med. 2021;27(12):2099. Epub 2021 Dec 10.


4. Planchard D, Besse B, Groen HJM, et al. Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. J Thorac Oncol. 2022;17(1):103. Epub 2021 Aug 26.


5. (Accessed on January 04, 2022).


6. (Accessed on January 04, 2022).


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