New Dosing Approved for Rylaze
A new dosing schedule was U.S. Food and Drug Administration (FDA) approved on Nov. 17, 2022, for Rylaze™ (asparaginase erwinia chrysanthemi [recombinant]-rywn – Jazz Pharmaceuticals) injection. Indicated as part of chemotherapy (chemo) regimens, it treats patients as young as one month old who have developed hypersensitivity to asparaginase products that are made from Escherichia coli (E. coli) during the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Originally intended for use every other day, its dosing can now be reduced to three times a week (on Monday and Wednesday mornings and Friday afternoons). Given by intramuscular (IM) injections, Rylaze is an enzyme that promotes the breakdown of asparagine, an amino acid that ALL and LBL cells need to survive, but which they cannot produce. The recommended dose when administered every other day is 25mg/m2. For the new schedule, the first two doses each week are the same at 25mg/m2, but Friday’s dose is doubled to 50mg/m2. Patients who have experienced allergic reactions, blood clots, hemorrhages, or pancreatitis when using any asparaginase product should not use Rylaze. Some patients in clinical trials had serious side effects that included changes in blood cell composition, liver damage, high blood glucose, low blood potassium, and severe infections. See full prescribing information for Rylaze here.
Blenrep Removed from Sale in the U.S.
The first B-cell maturation antigen (anti-BCMA) agent, Blenrep (belantamab mafodotin-blmf) injection, was given the FDA’s Accelerated Approval in August 2020. An antibody-drug conjugate, was indicated as monotherapy for relapsed or refractory multiple myeloma after four or more previous treatments. After the results of an FDA-required clinical trial, DREAMM-3, failed to show any significant advantage for Blenrep, its manufacturer, GSK, is withdrawing it from the U.S. market. In the study, Blenrep therapy was compared to treatment with Pomalyst® (pomalidomide) capsules plus dexamethasone. Although average progression-free survival (PFS) for patients in the Blenrep group was about five months longer (11.2 months vs. 7 months), overall survival (OS) averaged 21.2 months for Blenrep versus 21.1 months for the comparator drugs. Overall response rates (ORR) were about equal for the two treatment options, as well. Due to its potential to cause severe adverse effects on vision, Blenrep is dispensed only through a risk evaluation and mitigation strategy (REMS), which limits its prescribing to specially trained healthcare providers. Patients who currently use Blenrep may be able to continue treatment under a compassionate use program, but no new patients will be started on treatment with it. However, clinical studies for its use in combination with other cancer drugs, such as bortezomib plus dexamethasone, are ongoing.
On Nov. 22, 2022, the FDA issued a safety communication for patients who use Prolia® (denosumab) and who also need dialysis. Injected subcutaneously (SC) twice a year, Prolia decreases the breakdown of bone to treat osteoporosis. In a study of its use for patients who have advanced kidney disease that must be managed with dialysis, some patients developed hypocalcemia, possibly dangerously low levels of calcium in their blood. Patients using both should notify their healthcare providers right away if they experience new or worsening symptoms such as difficulty breathing, heart rhythm changes, muscle cramps, numbness, seizures, or vomiting. Health professionals are advised to watch calcium blood levels carefully for patients using both Prolia and dialysis and to assure that patients take supplements for calcium and vitamin D to maintain adequate blood calcium levels. More information is in the FDA’s notice.