Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.
Palmar-plantar erythrodysesthesia (PPE) is an uncommon adverse event with paclitaxel. We report a case of PPE due to paclitaxel to create awareness and review management strategies. A 61-year-old female with locally advanced lobular breast cancer was started on neoadjuvant chemotherapy with four cycles of dose-dense doxorubicin and cyclophosphamide. She completed these chemotherapy cycles uneventfully and was started on weekly paclitaxel (80mg/m 2 ) with a gap of two weeks. After receiving the sixth dose of paclitaxel, the patient presented with erythema, swelling, and discomfort of her hands and feet, interfering with her quality of life due to difficulty in carrying out daily routine activities. The changes were acute, occurred within a few days after the sixth dose of paclitaxel, and were consistent with PPE grade 2. Paclitaxel was discontinued, and the patient was switched to docetaxel every three weeks for two cycles. She used emollients and moisturizing creams for her local symptoms, after stopping paclitaxel, erythema, swelling, and discomfort of her hands and feet resolved within two weeks. She did not have a recurrence of these symptoms with docetaxel. Paclitaxel can cause PPE. Its incidence in the literature might be underreported. Discontinuation of paclitaxel can reverse skin toxicity and improve patient’s quality of life.
e20503 Background: Multiple Myeloma (MM) is treatable but an incurable hematological malignancy, requiring additional approaches such as maintenance therapy (MT) after autologous-stem cell transplantation. MT aids to achieve deepened response, sustained response and prolongs progression-free survival (PFS) but has a controversy over its overall survival (OS) benefit. Within the last decade, there have been innovative efforts tested for MT. We designed a systematic review to evaluate the current evidence on this topic. Methods: PubMed and Embase were searched for articles published on MT between 01/2010 and 12/2018 and PRISMA guidelines were used to evaluate 76,588 articles on PubMed and 1516 articles on Embase. Thirty-three articles were included in systematic review. Results: Thirteen articles were available on lenalidomide-MT whereas six articles each on thalidomide and proteasome inhibitors, five articles on combination therapy, two articles on miscellaneous and one article on elotuzumab were available, including trials and observational studies. MT (thalidomide 50 mg, lenalidomide 10 mg) was given for a variable period, commonly used till relapse, progression or unacceptable toxicity. Thalidomide showed consistent PFS-benefit but no OS benefit and had significant neurotoxicity, responsible for discontinuations or dose reductions. Lenalidomide had evidence for both, improved PFS and some evidence for better OS and had hematotoxicity, mainly neutropenia which required dose reductions. Secondary primary malignancies were more frequent with lenalidomide. Longer maintenance of lenalidomide was associated with more toxicity. Thalidomide-bortezomib combination had better PFS than thalidomide alone but no OS benefit. Bortezomib-MT improved OS in high-risk patients and renal failure and had dose-dependent toxicity. Bortezomib-MT after bortezomib-based induction was better than thalidomide-based-MT after cytotoxic induction. MT was associated with the achievement of negative MRD-status. Ixazomib was effective and feasible with improved PFS. Combination of bortezomib-lenalidomide-dexamethasone MT was beneficial in high-risk patients. Conclusions: MT improves PFS with limited evidence toward improved OS. For better outcomes, lenalidomide-based-MT should be given routinely; adjustment of dose might be required due to neutropenia. High-risk patients can get benefit from combination therapy. Role of combination MT needs to be further explored in large prospective studies.
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