pfs/efs/ttp os reference
13. references

1. Gay F, Palumbo A. Management of older patients with multiple myeloma. Blood Reviews 2011; 25: 65-73.  
2. Siegel DS, Desikan KR, Mehta J, et al. Age is Not a Prognostic Variable With Autotransplants for Multiple Myeloma. Blood. 1999; 93(1):51-54.  
3. Quach H, Miles Prince H, Spencer A. Managing multiple myeloma in the elderly: are we making progress? Expert Rev Hematol. 2011; 4(3): 301-315.  
4. Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-
Free and overall survival in elderly myeloma treated with novel agents: analysis 1175 patients. Blood. 2011; 117 (11): 3025-3031.  
5. Pulte D, Gondos A, Brenner H. Improvement in Survival of Older Adults with Multiple Myeloma:
Results of an Updated Period Analysis of SEER data. The Oncologist. 2011; 16: 1600-1603.  
6. Harousseau JL. Multiple Myeloma in the Elderly: When to Treat, When to go to Transplant.  
Oncology. 2010; 24(11): 1-11.  
7. Palumbo A, Mateos MV, Bringhen S, San Miguel JF. Practical management of adverse events in multiple myeloma: Can therapy be attenuated in older patients? Blood Reviews. 2011; 25: 181-191.  
8. Migkou M, Kastritis E, Roussou M et al. Short progression-free survival predicts poor overall Survival in older patients with multiple myeloma treated upfront with novel agent-based therapy. European Journal of Haematology. 2011; 87: 323-329.  
9. Bashir Q, Shah N, Wei W, et al. Feasibility of autologous hematopoietic stem cell transplant in Patients aged ≥70 years with multiple myeloma. Leukemia & Lymphoma. 2012; 53 (1): 118-122. 10. El Cheikh J, Kfoury E, Calmels B, et al. Age at transplantation and outcome after autologous Transplantation in elderly patients with multiple myeloma. Hematol Oncol Stem Cell Ther. 2011; 4(1): 30-36. 11. Cavo M, Pantani L, Petrucci MT. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012; epub ahead of print on April 12, 2012. 12. Ludwig H, Durie BGM, McCarthy P et al. IMWG consensus on maintenance therapy in multiple Myeloma. Blood. 2012; 119(13): 3003-3015. 13. McCarthy P, Owzar K, Hofmeister CC, et al. Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma. N Engl J Med. 2012; 336 (19): 1770-1781. 14. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL. Lenalidomide Maintenance After Stem-Cell Transplantation for Multiple Myeloma. N Engl J Med.  
2012 366(19): 1782-91. 15. Bensinger W, Jagannath S, Vescio R et al. Phase 2 study of two sequential three-drug Combinations containing bortezomib, cyclophosphamide, and dexamethasone, followed by bortezomib, thalidomide, and dexamethasone as frontline therapy for multiple myeloma. Brit J Haematology. 2009; 148: 562-568. 16. Hideshima T, Chauhan D, Podar K et al. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin Oncol. 2001; 28 (6): 607-612. 17. Dalton W. The tumor microenvironment: focus on myeloma. Cancer Treatment Reviews. 2003; 29 (Suppl I): 11-19. 18. Yarde D, Oliveira V, Mathews L et al. Cancer Res 2009; 69 (24): 9367-9375. 19. Landowski TH, Olashaw NE, Agrawal D et al. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-κB (RelB/p50) in myeloma cells. Oncogene. 2003; 22(16): 2417-21. 21. Giralt, S. Stem Cell Transplantation for Multiple Myeloma: Current and Future Status. ASH Education book; 2011(1): 191-196. 22. Barlogie B, Attal M, Crowley J et al. Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J of Clin Onc 2010; 28 (7): 1209-1214. 23. Barlogie B, Haessler J, Pineda-Roman et al. Completion of Pre-Maintenance Phases in Total Therapies 2 and 3 Improves Clinical Outcomes in Multiple Myeloma. Cancer 2008; 112 (12): 2720-2725. 24. Waheed S, Alsayed Y, Nair B, et al. Super-BEAM (SB): Incorporation of Bortezomib, Thalidomide, Dexamethasone, Cisplatin, and Rapamycin Into the BEAM Regimen for Multiple Myeloma (MM). 2009; ASH abstract 3421. 25. Martino M, Olivieri A, Offidani M et al. Addressing the questions of tomorrow: melphalan and new combinations as conditioning regimens before autologous hematopoietic progenitor cell transplantation in multiple myeloma. Expert Opin Investig Drugs 2013; 22(5): 619-634. 26. Lonial S, Kaufman J, Tighiouart M, et al. A Phase I/II trial combining high-dose melphalan and autologous transplant with bortezomib for multiple myeloma: a dose and schedule-finding study. Clin Cancer Res 2010; 16(20): 5097-86.  
27. Roussel M, Moreau P, Huynh A, et al. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 2010; 115(1): 32-37.  
28. Palumbo A, Avonto I, Bruno B, et al. Intermediate-Dose Melphalan (100 mg/m2)/Bortezomib/
Thalidomide/Dexamethasone and Stem Cell Support in Patients with Refractory or Relapsed Myeloma. Clin Lymph Myel 2006; 6(6): 475-477. 29. Miyamoto T, Yoshimoto G, Kamimura T et al. Combination of high-dose melphalan and Bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. Int J Hematology 2013; 98: 337-345. 30. Nishihori T, Alekshun T, Shain K, et al. Bortezomib salvage followed by a Phase I/II study of Bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma. Brit J Haematology 2012: 157: 553-563. 31. Wong Doo N, Thompson P, Prince HM, et al. Bortezomib with high dose melphalan conditioning for autologous transplant is safe and effective in patients with heavily pretreated and high risk multiple myeloma. Leuk & Lymph 2013 54(7): 1465-1472. 32. Pineda-Roman M, Zangari M, Haessler J, et al. Sustained complete remissions in multiple Myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Brit J Haematology 2008; 140: 625-634. 33. Cavallo F, Boccadoro M, and Palumbo A. Review of thalidomide in the treatment of newly diagnosed multiple myeloma. Ther Clin Risk Management 2007; 3(4): 543-552. 34. Van Rhee F, Szymonifka J, Anaissie E, et al. Total Therapy 3 for multiple myeloma: prognostic Implications of cumulative dosing and premature discontinuation of VTD maintenance Components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy. 14. Appendices
pfs/efs/ttp os reference
appendix i instructions for determining

For participants with weight <60kg, or who are under 5 ft tall, all doses will be based on actual body weight. For participants with weight >60kg and who are at least 5 ft tall, doses will be based on adjusted body weight, not to exceed a BSA of 2.0m2 during the D-PACE, transplant and consolidation phases.  
However, during the maintenance phase, adjusted body weight is preferred, but not required for participants with weight >60 kg and who are at least 5 ft tall.  
1. Actual Body Weight (ABW) is the weight in Kg. 2. Adjusted body weight (ABW): ABW = IBW + 0.4(actual weight - IBW). Ideal Body Weight (IBW):
Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet or 60 inches Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet or 60 inches
pfs/efs/ttp os reference
eortc qlq-c30 (version 3)

We are interested in some things about you and your health. Please answer all of the questions yourself by circling the number that best applies to you. There are no "right" or "wrong" answers. The information that you provide will remain strictly confidential. Please fill in your initials: ___________ Your birthdate (Day, Month, Year): ___________ Today's date (Day, Month, Year): ____________  
| ________________________________________________________________________________  Not at A Little Quite Very   All Bit a Bit Much 1. Do you have any trouble doing strenuous activities,  like carrying a heavy shopping bag or a suitcase? 1 2 3 4 2. Do you have any trouble taking a long walk? 1 2 3 4  3. Do you have any trouble taking a short walk outside of the house? 1 2 3 4  4. Do you need to stay in bed or a chair during the day? 1 2 3 4 5. Do you need help with eating, dressing, washing  yourself or using the toilet? 1 2 3 4 During the past week: Not at A Little Quite Very  All Bit a Bit Much 6. Were you limited in doing either your work or other daily activities? 1 2 3 4 7. Were you limited in pursuing your hobbies or other  leisure time activities? 1 2 3 4 8. Were you short of breath? 1 2 3 4 9. Have you had pain? 1 2 3 4   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 10. Did you need to rest?                                                                                 | 1      | 2      | 3       | 4    |
|-----------------------------------------------------------------------------------------------------------|--------|--------|---------|------|
| 11. Have you had trouble sleeping?                                                                        | 1      | 2      | 3       | 4    |
| 12. Have you felt weak?                                                                                   | 1      | 2      | 3       | 4    |
| 13. Have you lacked appetite?                                                                             | 1      | 2      | 3       | 4    |
| 14. Have you felt nauseated?                                                                              | 1      | 2      | 3       | 4    |
| 15. Have you vomited?                                                                                     | 1      | 2      | 3       | 4    |
| 16. Have you been constipated?                                                                            | 1      | 2      | 3       | 4    |
| Please go on to the next page                                                                             |        |        |         |      |
| During the past week:                                                                                     | Not at | A      | Quite a | Very |
|                                                                                                           | All    | Little | a Bit   | Much |
| 17. Have you had diarrhea?                                                                                | 1      | 2      | 3       | 4    |
| 18. Were you tired?                                                                                       | 1      | 2      | 3       | 4    |
| 19. Did pain interfere with your daily activities?                                                        | 1      | 2      | 3       | 4    |
| 20. Have you had difficulty in concentrating on things,  like reading a newspaper or watching television? | 1      | 2      | 3       | 4    |
| 21. Did you feel tense?                                                                                   | 1      | 2      | 3       | 4    |
| 22. Did you worry?                                                                                        | 1      | 2      | 3       | 4    |
| 23. Did you feel irritable?                                                                               | 1      | 2      | 3       | 4    |
| 24. Did you feel depressed?                                                                               | 1      | 2      | 3       | 4    |
| 25. Have you had difficulty remembering things?                                                           | 1      | 2      | 3       | 4    |
| 26. Has your physical condition or medical treatment  interfered with your family life?                   | 1      | 2      | 3       | 4    |
| 27. Has your physical condition or medical treatment  interfered with your social activities?             | 1      | 2      | 3       | 4    |
| 28. Has your physical condition or medical treatment  caused you financial difficulties?                  | 1      | 2      | 3       | 4    |  
For the following questions please circle the number between 1 and 7 that best applies to you 29. How would you rate your overall health during the past week? 1 2 3 4 5 6 7 Very poor Excellent 30. How would you rate your overall quality of life during the past week? 1 2 3 4 5 6 7 Very poor Excellent
© Copyright 1995 EORTC Quality of Life Group. All rights reserved. Version 3.0
pfs/efs/ttp os reference
eortc qlq - my20

Patients sometimes report that they have the following symptoms or problems. Please indicate the extent to which you have experienced these symptoms or problems during the past week. Please answer by circling the number that best applies to you.  
| During the past week:                              | Not at   | A      | Quite   | Very   |
|----------------------------------------------------|----------|--------|---------|--------|
|                                                    | All      | Little | a Bit   | Much   |
| 31. Have you had bone aches or pain?               | 1        | 2      | 3       | 4      |
| 32. Have you had pain in your back?                | 1        | 2      | 3       | 4      |
| 33. Have you had pain in your hip?                 | 1        | 2      | 3       | 4      |
| 34. Have you had pain in your arm or shoulder?     | 1        | 2      | 3       | 4      |
| 35. Have you had pain in your chest?               | 1        | 2      | 3       | 4      |
| 36. If you had pain did it increase with activity? | 1        | 2      | 3       | 4      |
| Page 73 of 74                                      |          |        |         |        |  
| 37. Did you feel drowsy?                                                                      | 1      | 2      | 3     | 4    |
|-----------------------------------------------------------------------------------------------|--------|--------|-------|------|
| 38. Did you feel thirsty?                                                                     | 1      | 2      | 3     | 4    |
| 39. Have you felt ill?                                                                        | 1      | 2      | 3     | 4    |
| 40. Have you had a dry mouth?                                                                 | 1      | 2      | 3     | 4    |
| 41. Have you lost any hair?                                                                   | 1      | 2      | 3     | 4    |
| 42. Answer this question only if you lost any hair:  Were you upset by the loss of your hair? | 1      | 2      | 3     | 4    |
| 43. Did you have tingling hands or feet?                                                      | 1      | 2      | 3     | 4    |
| 44. Did you feel restless or agitated?                                                        | 1      | 2      | 3     | 4    |
| 45. Have you had acid indigestion or heartburn?                                               | 1      | 2      | 3     | 4    |
| 46. Have you had burning or sore eyes?                                                        | 1      | 2      | 3     | 4    |
| Please turn to next page                                                                      |        |        |       |      |
| During the past week:                                                                         | Not at | A      | Quite | Very |
|                                                                                               | All    | Little | a Bit | Much |
| 47. Have you felt physically less attractive as a result  of your disease or treatment?       | 1      | 2      | 3     | 4    |
| 48. Have you been thinking about your illness?                                                | 1      | 2      | 3     | 4    |
| 49. Have you been worried about dying?                                                        | 1      | 2      | 3     | 4    |
| 50. Have you worried about your health in the future?                                         | 1      | 2      | 3     | 4    |