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Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Lenalidomide (Figure 9.9) is a close analog of thalidomide, differing only in removal of the C3-carbonyl and addition of a C4-amino group. Like thalidomide, it is also a racemic mixture. Not surprisingly, it has similar properties to thalidomide and is an immunomodulating agent with antineoplastic, antiangiogenic, and pro-erythropoietic properties. Lenalidomide is used in combination with dexamethasone for the treatment of multiple myeloma in patients who have already received at least one previous therapy. It is also licensed for the treatment of transfusion-dependent anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with an isolated 5q cytogenetic deletion abnormality when other treatment options are insufficient or inadequate.
Multiple Myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Grade III–IV neuropathy with bortezomib has been significantly reduced by switching from intravenous to subcutaneous injection and a weekly schedule without reduced efficacy. Other side effects with bortezomib include gastrointestinal toxicity, thrombocytopenia, herpes zoster, and hypotension. Both thalidomide and lenalidomide are prothrombotic, and all patients must be assessed for thrombotic risk with a view to starting on appropriate prophylaxis which is typically either prophylactic-dose low-molecular-weight heparin or aspirin. Thalidomide also causes constipation, neuropathy, and somnolence. Lenalidomide although derived from thalidomide does not cause these side effects but does cause fatigue and myelosuppression and requires dose reduction in renal failure. With daratumumab the most common side effect is typically a mild infusional toxicity with the first dose.
Specific Current Therapy for Myelomas
Published in Tariq I Mughal, John M Goldman, Sabena T Mughal, Understanding Leukemias, Lymphomas, and Myelomas, 2017
Tariq I Mughal, John M Goldman, Sabena T Mughal
A potential recent challenge for patients receiving any of the novel drugs for first line therapy has been the mobilization of stem cells for a subsequent autologous SCT. It appears that that all three drugs can reduce the peripheral stem cell (CD34 positive cells) concentration, with lenalidomide probably reducing them to a greater extent. Specialists therefore often harvest the stem cells earlier than with conventional chemotherapy and most use cyclophosphamide and granulocyte-colony stimulating factors to optimize the harvest. We will discuss this further in chapter 11.
A review of the current status of lenalidomide maintenance therapy in multiple myeloma in 2022
Published in Expert Review of Anticancer Therapy, 2022
Ravi Kumar Gupta, Ashish Gupta, Jens Hillengass, Sarah A. Holstein, Vera J. Suman, Alankrita Taneja, Philip L. McCarthy
The concept of maintenance therapy in MM has been established for more than 30 years. Early maintenance treatments such as chemotherapy, interferon, corticosteroids, and thalidomide saw limited use due to toxicities. Lenalidomide is an IMiD that directly induces MM cell apoptosis and inhibits cell proliferation by binding to cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase. Lenalidomide treatment results in proteasomal degradation of CK1α protein and other transcription factors [8–10]. Lenalidomide promotes apoptosis of myeloma cells, inhibits growth factors, prevents myeloma cell adherence to bone marrow stromal cells, and suppresses angiogenesis [11]. Not only does it have a direct anti-tumor effect, it also impacts the immune system. A study by Noonan et al. demonstrated that it augments vaccine responses and endogenous anti-tumor immunity [12]. Lenalidomide introduction into the maintenance setting transformed the field by reducing the risk of relapse while being well-tolerated and maintaining quality of life. In June 2006, the US Food and Drug Administration (FDA) initially approved the lenalidomide (CC-5013, Revlimid®) (Celgene Corporation, Summit, NJ, USA) for use in combination with dexamethasone for patients with MM following at least one prior therapy. In 2015, regulatory approval was extended to newly diagnosed MM (NDMM) patients. Two years later, in 2017, lenalidomide was approved as maintenance therapy for patients with MM after ASCT, based on the findings of multiple randomized clinical trials (RCTs) such as CALGB 100104, IFM2005-02, and GIMEMA RV-MM-PI-209 trials [13].
Economic evaluation of polatuzumab-bendamustine-rituximab vs. tafasitamab-lenalidomide in transplant-ineligible R/R DLBCL
Published in Journal of Medical Economics, 2021
Matthias Calamia, Ali McBride, Ivo Abraham
In L-Mind, the Tafa-L regimen was comprised of tafasitamab and lenalidomide co-administration for up to 12 cycles of 28 days each15. After 12 cycles lenalidomide was discontinued and tafasitamab monotherapy was continued until disease progression. For the first three cycles, a weekly dose of 12 mg/kg of tafasitamab was administered IV, with an additional loading dose on day 4 of cycle 1 for a total of five administrations in cycles 1 and 4 in cycles 2 and 3. From cycle 4, tafasitamab was administered once every 14 days for a total of two administrations per cycle. Patients self-administered oral lenalidomide at a dose of 25 mg/day on days 1–21 of each 28-day cycle and this for 12 cycles. Premedication included diphenhydramine, acetaminophen, famotidine, dexamethasone, and aspirin. Compazine was administered PRN for nausea and vomiting.
Advances in maintenance strategy in newly diagnosed multiple myeloma patients eligible for autologous transplantation
Published in Expert Review of Hematology, 2020
Ahsan Wahab, Abdul Rafae, Muhammad Salman Faisal, Kamran Mushtaq, Hamid Ehsan, Maria Khakwani, Afia Ashraf, Tayyab Rehan, Zahoor Ahmed, Zunairah Shah, Aslam Khan, Faiz Anwer
Lenalidomide has greater rates of hematologic AEs (48% vs 17% in CALGB-100,104, 69% vs. 35% in IFM-2005-02) and thrombosis (6.2% vs. 2% in IFM-2005-02), when compared with placebo [11,12,23,31]. Neutropenia and thrombocytopenia are the most common hematologic AEs of lenalidomide that often require dose reductions [28,34]. Infections and dermatologic AEs are also common [33]. Goldschmidt et al. noted more frequent toxicity with longer use of lenalidomide compared to limited use [27]. In a real-world study, the average duration of lenalidomide spanned up to 33.2 months and 50% of patients required dose reductions. Common reasons of dose reductions were cytopenia, rash, fatigue, and infection. Progressive disease was a more common cause of lenalidomide discontinuation than its AEs [34].