1 / 34

Case 1

Case 1. 57 yr old male. Rib pain – X-ray revealed lytic lesion, biopsy: plasma cells . Hgb 11.6 g/dL, creatinine 0.8 mg/dL, Ca++ 9.0 mg/dL . Bone marrow 33% +CD38, +CD138, -CD56, λ -, κ + PC

aysel
Download Presentation

Case 1

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Case 1 • 57 yr old male • Rib pain – X-ray revealed lytic lesion, biopsy: plasma cells • Hgb 11.6 g/dL, creatinine 0.8 mg/dL, Ca++ 9.0 mg/dL • Bone marrow 33% +CD38, +CD138, -CD56, λ -, κ + PC • T. Protein 7.5 g/dL, Albumin 3.0 g/dL, M-protein 3.2 g/dL: IgG κ, Bence Jones Protein 10 mg/day • Free λ 6.39 mg/L Free κ 24.27 mg/L Free κ: λ 3.798 • β2M 1.8 mg/L Alb 3.5g/dL: ISS stage I • Bone survey: multiple small lytic lesions in ribs, skull and right femur

  2. Case 1 • Patient started on induction with bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11 lenalidomide 25 mg po daily x 14 days dexamethasone 20 mg day 1,2,4,5,6,7,8,9,11,12

  3. What would you do regarding thromboembolism prophylaxis for lenalidomide? • No intervention 2. Aspirin 81 mg po daily • 3. Enoxaparin or equivalent 40 mg subcutaneous daily • 4. Warfarin adjusted to keep INR 2-3 • 5. Warfarin 1.25 mg po daily

  4. Thalidomide & Lenalidomide Thromboprophylaxis Individual Risk Factors Actions Obesity Previous VTE Central Venous Catheter, Pacemaker Associated Disease Cardiac Chronic Renal Disease Diabetes Acute Infection Immobilization Surgery Gen. Surgery Any Anesthesia Trauma Medications ESA's Blood Clotting Disorders 0 or 1 Risk Factor: ASA 81-325 mg po daily • > 2 Risk Factors: • LMWH (Enoxaparin 40mg daily or equivalent) • Warfarin (Target INR 2-3) Myeloma-Related Risk Factors Diagnosis Hyperviscosity Myeloma Therapy • LMWH (Enoxaparin 40mg daily or equivalent) • Warfarin (Target INR 2-3) High-Dose Dexamethasone Doxorubicin Multi-Agent Chemotherapy Palumbo et al, Leukemia 2008, 22: 414-423

  5. Randomized Trial of Aspirin, warfarin, Enoxaparin during thalidomide-dexamethasone combinations for myeloma P not significant compared with enoxaparin Palumbo et al. J Clin Oncol. 2011;29(8):986-93:311-319.

  6. Case 1 • Patient started on induction with bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11 lenalidomide 25 mg po daily x 14 days dexamethasone 20 mg day 1,2,4,5,6,7,8,9,11,12 • After Cycle 2, the M-protein is 1.3 g/dL • After Cycle 2, he complains of tingling in fingers and toes, but denies any pain

  7. What would you do regarding the neuropathy? • Continue same doses of chemotherapy 2. Change bortezomib to subcutaneous • 3. Change bortezomib to weekly • 4. Reduce bortezomib to 1.0 mg/m2 • 5. Stop bortezomib

  8. NCI CTCAE v 4.0 Peripheral Neuropathy CTCAE = common terminology criteria for adverse events; NCI = National Cancer Institute; aThese definitions are not specific to MM and the classification of a PN event as grades 1–4 may be subject to investigator bias. Richardson et al. Leukemia. 2012;26:595-608.

  9. Guidelines for Bortezomib-Induced Neuropathy Guidelines for Thalidomide-Induced Neuropathy Mohty et al. Haematolohica. 2012;95:311-319.

  10. Subcutaneous Vs. Intravenous Bortezomib IV SC 2 ways to reconstitute a 3.5-mg vial of bortezomib Add 3.5 mL 0.9% sodium chloride Add 1.4 mL 0.9% sodium chloride 1 mg/mL 2.5 mg/mL IV = intravenous; SC = subcutaneous Bortezomib (Velcade®) Package Insert. 2012. Moreau P et al. Lancet Oncol. 2011;12:431-440

  11. Case 1 • Patient continues on induction with bortezomib 1.3 mg/m2 SC on days 1, 4, 8, 11 lenalidomide 25 mg po daily x 14 days dexamethasone 20 mg day 1,2,4,5,6,7,8,9,11,12 • During cycle 4, Day 8 of therapy the patient’s platelet count is 33,000

  12. What would you do regarding the thrombocytopenia? • Continue same doses of chemotherapy 2. Reduce bortezomib to 1.0 mg/m2 • 3. Reduce lenalidomide to 15 mg po daily x 14 days • 4. Stop bortezomib • 4. Stop lenalidomide

  13. Guidelines for Bortezomib-Induced Cytopenias If several consecutive doses held and combined with other myelosuppressive agent consider dose adjustment of other agent (melphalan, lenalidomide, cyclophosphamide, etc) Guidelines for Lenalidomide-Induced Cytopenias

  14. Case 1 • Patient continues on induction with bortezomib 1.3 mg/m2 SC on days 1, 4, 8, 11 lenalidomide 25 mg po daily x 14 days dexamethasone 20 mg day 1,2,4,5,6,7,8,9,11,12 • After Cycle 4, he still complains of only slight tingling in fingers and toes and denies any pain • After Cycle 5, the M-protein is 0.2 g/dL • After Cycle 5, he now complains of pain w/ numbness in fingers and toes and has difficulty buttoning his shirt

  15. What would you do regarding the neuropathy? • Continue same doses of chemotherapy 2. Change bortezomib to subcutaneous • 3. Change bortezomib to weekly • 4. Reduce bortezomib to 1.0 mg/m2 • 5. Stop bortezomib

  16. NCI CTCAE v 4.0 Peripheral Neuropathy Guidelines for Bortezomib-Induced Neuropathy CTCAE = common terminology criteria for adverse events; NCI = National Cancer Institute; aThese definitions are not specific to MM and the classification of a PN event as grades 1–4 may be subject to investigator bias. Richardson et al. Leukemia. 2012;26:595-608.

  17. Case 1 • The patient decides to proceed to myeloablative therapy + autologous stem cell transplant (AuSCT) • Therapy is held for 2.5 weeks and an attempt to harvest stem cells with G-CSG (filgastrim) alone is unsuccessful

  18. What would you do next? • Tell the patient that harvest was unsuccessful and continue chemotherapy 2. Attempt harvest after cyclophosphamide mobilization therapy (+/- mobizil)

  19. Case 1 • Autologous stem cell harvest is successful after cyclophosphamide chemomobilization and the patient proceeds with high-dose melphalan + autologous stem cell transplant (AuSCT) • 3 months post- AuSCT the patient is started on lenalidomide maintenance therapy 10 mg po daily

  20. Case • 3 months post- AuSCT the patient restarts zoledronic acid monthly after previously being cleared by the dentist • M-protein reduces to 0, but immunofixation remains positive at 6 months post-AuSCT

  21. Case • The patient develops right lower jaw pain and is evaluated by the dentist and has an abscess, which responds to antibiotic therapy, but the tooth needs extraction.

  22. What would you do regarding the extraction? • Have the tooth extracted immediately. 2. Stop zoledronic acid and have the tooth extracted immediately. • 3. Hold zoledronic acid, treat the tooth, wait at least 1 month, if possible, and extract the tooth.

  23. Case • The patient has the tooth extracted and after 3 months zoledronic acid is restarted. • The patient continues on lenalidomide 10mg/d in near CR by SPEP • 1 year post-AuSCT the patient’s creatinine begins to rise and is 1.97mg/dL (creatinine clearance 33 ml/min) • 24 hr UPEP reveals a rise in total protein to 453 mg/d (Bence Jones protein 7 mg/d) : previous total proteinuria 87 mg/d with 5 mg Bence Jones protein

  24. What would you do regarding the creatinine? • Change therapy the patient’s disease is progressing 2. Stop zoledronic acid and repeat UPEP in 1 month • 3. Dose adjust lenalidomide

  25. Creatinine Clearance (m/min) Lenalidomide Dose (mg) > 30 - 50 10 mg/Day < 30, NOT on dialysis 15 mg q48 hours 5 mg/D after dialysis On dialysis Lenalidomide • Celgene Product Information available at www. Revlimid.com/pdf/revlimid/pl.pdf

  26. Case • 1 month later the total urine protein is 110 mg/d and zoledronic acid is restarted with no further increase in proteinuria • The creatinine improves to 1.3 mg/dL . • On physical exam the patient has a 4-5 mm fullness on the left pharyngeal arch.

  27. Case • PATHOLOGY REPORT • WIDE LOCAL EXCISION LESION LEFT SOFT PALATE: • POLYMORPHOUS ADENOCARCINOMA. • Tumor size = 1.7 cm • Perineural invasion: PRESENT, MULTIFOCAL • Peripheral margin: FOCALLY CLOSE < 2 MM • The patient begins a 6 week cycle of radiotherapy with curative intent of the head and neck tumor – lenalidomide placed on hold • 2 months later the SPEP reveals an M-protein of 0.4 mg/dL

  28. You confirm relapse with a second what therapy do you start? • Restart lenalidomide 10 mg po daily 2. Start lenalidomide 25 mg po x 21 d + dexamethasone 40 mg po weekly • 3. Bortezomib 1.0 mg/m2 by subcutaneous injection weekly • Carfilzomib 20 mg/m2 d 1,2,8,9,15,16 • Dexamethasone 4 mg IV d1 • 250 cc NS before carfilzomib • 5. Pomalidomide 4 mg po daily x 28 day cycles + Dexamethasone 40 mg po weekly

  29. Secondary Primary Malignancies (SPMs): Lenalidomide CALBG100104 vs. SEER McCarthy PL, et al. NEJM, 2012 Attal M, et al. NEJM, 2012

  30. Case • The patient begins carfilzomib, but on day 1 develops dyspnea with mild chest pain. • Furosemide 20 mg IV improves the dyspnea • During the next cycle pre-hydration is decreased to 125 cc’s prior to carfilzomib, which is well tolerated.

  31. Carfilzomib Hematologic Toxicity Dose Reductions Guidelines for Carfilzomib-Induced Renal Insufficiency Jagannath et al. Clinical Lymphoma, Myeloma &Leukemia. 12;310-18, 2012.

  32. Doxil® (doxorubicin) [prescribing information]. Raritan, NJ: Centocor Ortho Biotech Products, LP; 2010; Revlimid® (lenalidomide) [prescribing information]. Summit, NJ: Celgene; 2010; Thalomid® (thalidomide) [prescribing information]. Summit, NJ: Celgene; 2010; Velcade® (bortezomib) [prescribing information]. Cambridge, MA: Millennium Pharmaceuticals, Inc; December 2010.

  33. Considerations When Treating Older Individuals Palumbo et al. Blood. 2011;118:4519-4529.

More Related