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  1. ASH Highlights 2011 San Diego, California

  2. Lymphoma

  3. Lymphoma in Pregnancy: Excellent Foetal Outcomes and Maternal Survival in a Large Multicenter Analysis Advani et al, #94 • Retrospective analysis of patients with Hodgkin Lymphoma (HL) or non-Hodgkin Lymphoma (NHL) • Standard chemotherapy for HL/NHL administered (minus antimetabolites) • Typical regimens – ABVD, CHOP+/- R,CODOX-M/IVAC

  4. Summary of Results • 48 pts had chemo initiated at a median of 25 wks (13-37) • 79% in 2nd trimester • Chemo administered with minimal pre-term complications • 1 still birth following 1x R-CHOP • 1 case of microcephalus following 4x CHOP • No other malformations detected • Median birth weight of infants similar between patients who received chemo during pregnancy vs. those who deferred treatment until after birth • Median f/u: 41 months • Approach associated with expected lymphoma related outcomes PFS, OS • Uncommon extra nodal sites included vaginal and breast

  5. Relevance to Practice • This retrospective analysis will provide some confidence that standard treatment may be administered to pregnant women with HL and NHL • Questions remain about long-term effects and patients who require anti-metabolite chemo, particularly in early stage pregnancy

  6. Phase 2 Trial of Alisertib (MLN8237), An Investigational, Potent Inhibitor of Aurora A Kinase (AAK), in Patients (pts) with Aggressive B- and T-Cell Non-Hodgkin Lymphoma (NHL),  Friedberg et al #95 • 48 patients with relapsed/refractory aggressive B cell (MCL, DLBCL, BL, transformed FL)+ T-cell lymphoma • Alisertib 50mg BD x 7d (21d cycle) • 41 response evaluable • Median of 3 prior treatments • ORR 32%, CR 12% • ORR T-Cell: 57%, MCL: 23%, DLBCL: 20% • Response seen in all patients • Major AEs: neutropenia, thrombocytopenia, stomatitis • Generally well tolerated, AEs manageable with dose reduction however 50% of pts required dose reduction

  7. Relevance to Practice • Alisertib has activity in aggressive lymphoma in patients who are heavily pre-treated • No current impact to UK practice but one to watch, future trials include: • SWOG phase III study in relapsed/refractory T-cell lymphoma • Millennium sponsored phase III randomised relapsed/refractory T-cell trial • B-cell study planned

  8. Analysis of Patients with Common Peripheral T-Cell Lymphoma Subtypes From a Phase 2 Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma, Coiffier et al #591 Phase 2, open label, single arm study Romidepsin 14 mg/m² IV infusion over 4 hours on days 1, 8 and 15 of a 28 day cycle for 6 cycles Primary endpoint: rate of CR n = 130, median f/u: 21 months, median of 2 prior therapies ORR: 28% CR/CRu: 16% PR: 12% ORR + SD ≥90 days: 46%

  9. Results of E4402 (RESORT): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Low Tumour Burden Follicular Lymphoma, Kahl et al #LBA6 RITUXIMAB (R) 375mg/m² q3months UNTIL PROGRESSION n=140 CR or PR RITUXIMAB (R) 375mg/m² weekly (x4) INDUCTION n=384 Randomisation n=274 NO TREATMENT n=134 On progression RE-INDUCT (R x 4) • Previously untreated low tumour burden follicular lymphoma pts • Major definition of treatment failure: • Progression within 6 months of R or failure to achieve CR while on R • Re-treatment group received 4.5 doses R • Maintenance group received 15.8 doses R

  10. Results and Relevance to Practice • Primary Endpoint: Time to Treatment Failure – no difference • Secondary Endpoints: • Time to first cytotoxic – longer in maintenance arm (p=0.03) • QoL – not fully analysed but not expected to differ • No evidence of superiority of maintenance and much more expensive • Current practice not expected to change until OS data available • Biomaker evaluation may help to select patients who are likely to respond to rituximab induction therapy • Note: this is only low tumour burden population

  11. A Phase 3 Randomized Intergroup Trial (SWOG S0016) of CHOP Chemotherapy Plus Rituximab Vs. CHOP Chemotherapy Plus Iodine-131-Tositumomab for the Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphoma (FL), Press et al #98 5 days at 3 week intervals • 554 patients with advanced stage (bulky stage II, III or IV) evaluable FL of any grade (1, 2, or 3), with no prior therapy • All patients received CHOP chemo • 750mg/m2 cyclophosphamide • 50mg/m2 doxorubicin • 1.4mg/m2 vincristine • 100mg predisolone • Arm 1 – CHOP-R (x 6 cycles) • + 6 doses of rituximab (375mg/m2) on days 1, 6, 48, 90, 134 and 141 • Arm 2 – CHOP-RIT (x 6 cycles) • + dosimetric infusion of tositumomab/iodine I-131 tositumomab and then 1-2 weeks later a therapeutic infusion of I-131-tositumomab labelled with sufficient I-131 (median 85 mCi) to deliver a total body dose of 75 cGy (CHOP-RIT)

  12. Summary of Results • No statistically significant differences in PFS, OS, or serious toxicities • However, PFS and OS are outstanding with either of the two  regimens with median times to progression not yet reached for either treatment • Future studies needed to assess whether combining CHOP-R with RIT consolidation and with maintenance rituximab will confer additive benefit • Currently being evaluated in a follow-up trial (SWOG protocol S0801)

  13. Relevance to Practice Trial recruited 2001-08: during this period, rituximab+chemo and then maintenance rituximab have been recommended as standard practice for first-line treatment of FL in the UK. Tositumumab + CHOP is certainly as good as CHOP-R in first line treatment of FL. However there would need to be further study to see if tositumumab + CHOP produces remission rates comparable to CHOP-chemo followed by maintenance rituximab. Tositumumab has to be given in specialist facilities which are not widely available in the UK. Rituximab can be given in hospital and homecare settings: this probably gives the edge to rituximab for first-line treatment of FL.

  14. Fractionated 90y Ibritumomab Tiuxetan (ZevalinTM) Radioimmunotherapy As An Initial Therapy of Follicular Lymphoma (FL) – First Results From a Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria, Illidge et al #102 • 74 patients with untreated FL (grade 1, 2 or 3a) and at least 1 criterion of high tumour burden received: • 2 x doses of 90Y-ibritumomab tiuxetan (11.1 MBq/kg) given 8-12 weeks apart • Patients with > 20% bone marrow involvement (BM) with lymphoma received 4 weekly infusions rituximab (375 mg/m2) and proceeded to fractionated RIT, only if a repeat BM biopsy demonstrated clearing of lymphoma with ≤ 20% involvement • Primary endpoint: end of treatment response (EOR) of ITT population • Assessed 12 weeks after last 90Y-ibritumomab tiuxetan infusion (21 weeks after treatment start) • Secondary endpoints: Safety & PFS

  15. Summary of Results • 2/72 patients did not have recorded response data • EOR was 95.7% (67/70) with Cru of 57.1% (40/71) • 6 patients subsequently improved response: • ORR = 97.1% (68/70) (95% CI 90.0% - 99.7%) • Cr/Cru = 64.3% (45/70) (95% CI 51.9% - 75.4%) • PFS = 67% • Based on median follow up of 1.52 years (range 0.13 – 3.68 years) • Most common toxicities were haematological and occurred after the first 90Y-ibritumomab tiuxetan dose • Transient neutropenia 20.8%, 18 days median duration) • Thrombocytopenia (20.8%; 20 days median duration)

  16. Relevance to Practice • Zevalin appears to be effective and reasonably well tolerated in this group of patients • Further studies are required; • This is a relatively small trial size (n = 72) • Phase II data - The trial did not compare this drug against any other treatment • As with other radioimmunotherapies, specialist facilities are required to give Zevalin • This limits the usefulness of this drug in the UK.

  17. The Addition of Rituximab to Fludarabine and Cyclophosphamide (FC) Improves Overall Survival in Newly Diagnosed Mantle Cell Lymphoma (MCL): Results of the Randomised UK National Cancer Research Institute (NCRI) Trial Rule et al #440 • 370 newly diagnosed, mantle cell lymphoma patients • Phase II trial initiated in 2002, extended to phase III in 2006 • Up to 8 x cycles (28 days) • Fludarabine po 40mg/m2 D1 – D3 • Cyclophosphamide po 250mg/m2 D1 – D3 • Randomised to + / - rituximab iv 375mg/m2 D1 • Median age was 66 years (range 36 – 88) • 76% male patients • 78% and 72% respectively received 4 or more cycles of FCR/FC

  18. Summary of Results • Patients in the FCR arm had a longer PFS and OS compared to FC • Median follow up 38.8 months

  19. Adverse events • The major toxicities were haematological • Significantly more patients in the FCR arm experienced grade 3 or 4 Leucopoenia and Thrombocytopenia however the numbers of grade 4 were not significantly different • Combined grade III/IV toxicity showed 23.3% thrombocytopenia, 45.8% leucopoenia, 12.9% anaemia and 51.4% neutropenia • 11.8% of patients had significant infections • Renal toxicity was modest. • 1 patient experienced grade III but there was no grade IV toxicity • 29% FCR patients and 24% of FC patients died of other causes • Almost half were infection related • 11 patients died of a second malignancy (4/11 AML)

  20. Relevance to practice • The addition of rituximab resulted in a significant increase in overall survival • FC is not standard treatment across the UK in all MCL patients • Most UK centres are already using rituximab for MCL • Results may support applications to the CDF for centres currently unable to use • Acceptable toxicity in patients <70 years • Rituximab is not licensed in this setting • Unlikely to be considered by NICE

  21. Phase II Study of Ofatumumab in Combination with ICE or DHAP Chemotherapy in Relapsed or Refractory Aggressive B-Cell Lymphoma Prior to Autologous Stem Cell Transplantation (ASCT) Matasar et al #957 • 61 pts with DLBCL, 36 pts with follicular or transformed follicular lymphoma randomised to receive ofatumumab with ICE or DHAP • Median age 54yrs • Must have previously received R+anthracycline 1st line • Chemotherapy regimen selected by investigator • Study not powered to look at the difference between regimens • Primary endpoint: ORR of ofatumumab + chemo

  22. Results and Relevance to Practice • ORR shows that combination is effective • However, a large randomised trial against R + chemo in relapsed patients is required with multiple arms to determine the most effective regimen for relapsed patients

  23. Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma, Younes et al #955 • Study aimed to assess safety of brentuximab vedotin (B) in combination with ABVD or AVD and determine MTD in combination • 44 pts, 18-60 yrs, treatment naive with stage IIa bulky or IIb-IV hodgkin lymphoma • ABVD/AVD administered for 6 x 28d cycles • B dose escalation 0.6mg/kg to 1.2mg/kg • MTD not reached therefore 1.2mg/kg every 2 weeks is escalation phase dose • Pulmonary toxicity of ABVD was increased when combined with B but not with AVD • 1.2mg/kg B + AVD is the combination that will be used in future trials • Watch this space!

  24. Brentuximab Vedotin (SGN-35) Enables Successful Reduced Intensity Allogeneic Hematopoietic Cell Transplantation (RIC allo-HCT) in Relapsed/Refractory Hodgkin Lymphoma Chen et al #664 • Retrospective analysis of 46 relapsed/refractory HL pts treated with the antibody-drug conjugate, brentuximab-vedotin • 16/46 (34.8%) patients subsequently underwent RIC allo-HSCT • 14/16 had received prior autologous HSCT • Pre-treated population (2-6 prior lines of therapy) • 1 yr OS: 100% • Brentuximab did not delay engraftment times post HSCT and the procedure was well tolerated • Disease status at time of transplant: • 7 x CR, 6 x PR, 2 x PD (no bulky disease), 1x SD

  25. Relevance to Practice • Strengths and Weaknesses • Demonstrates that previously reported efficacy (75% RR) can be translated into a chance of cure by allowing allo-HSCT • Not compared to standard UK relapse treatment (ChlVPP or GemP) • Unclear what happened to 30 patients who did not receive allo-HSCT • Treatment with brentuximab could secure sufficient disease control to allow HSCT in the small cohort of patients with HL refractory to current standard therapies • Likely to be extremely expensive – could this be a CDF therapy?

  26. LEUKAEMIA

  27. Initial Findings From the PACE Trial: A Pivotal Phase 2 Study of Ponatinib in Patients with CML and Ph+ ALL Resistant or Intolerant to Dasatinib or Nilotinib, or with the T315I Mutation, Cortes et al #109 Single arm study of ponatinib, a multikinase inhibitor that accommodates T315I mutations (n=449) This is only a phase II study with no control arm, the wide patient mix could be a strength or weakness Very early follow up therefore low response rates

  28. Relevance to Practice Current data is very early however clinicians will want rapid access to ponatinib for their resistant/T315I mutated patients Should we expect phase III data or will phase II be enough? A treatment for 2nd generation resistant and T351I mutated patients is needed – could this be it? Expect ponatinib to be coming to a pharmacy near you within 18 months!

  29. Imatinib Dose Interruption in Responding CML Patients Is Associated with Characteristic BCR-ABL Kinetics, Which Could Help to Differentiate Non-Adherence From Drug Resistance, Branford et al #111 Study aimed to distinguish if loss of response can be related to biological resistance or adherence using BCR-ABL doubling time (DT) n=539 achieving MCyR DT: 62d for 10-20% of no dose days

  30. Relevance to Practice Doubling time of 9 days suggests non-adherence if patient is still in CP Calculating doubling time may indicate a non-adherent patient at no extra expense to the NHS There is a role for pharmacists to identify non-adherent patients although poorly adherent patients may be harder to identify

  31. Multiple Low Level Mutations Identifies Imatinib Resistant CML Patients At Risk of Poor Response to Second-Line Inhibitor Therapy, Irrespective of the Resistance Profile of the Mutations, Parker et al #111 • Mass spectrometry BCR-ABL mutation assay • Detecting 90% of all mutations (31) • Detection limit <0.5% compared to 10-20% in direct sequencing methods • Could sensitive mutational analysis before 2° TKI therapy predict response? • 132 low level mutations not detected by direct sequencing • Up to 10% of mutations per patient • Previously demonstrated (JCO 2011) that use of resistant TKI can select for these mutations • Number of mutations is important even if not conferring resistance to TKI

  32. Results and Relevance to Practice • n=175 - no nilotinib/dasatinib mutation • 19% detected with mass spectrometry • 9% by direct sequencing • 0/1 mutations: 50% CCyR, 31% MMR • ≥2 mutations: 21% CCyR, 6% MMR • 56% developed new mutations • Study provides evidence that prediction of patient response to 2° TKIs can be achieved • Allows provision of alternative treatments to those who will not respond • Preventing wasted money on therapies that will not work in patients with mutations

  33. Lenalidomide and Rituximab for the Initial Treatment of Patients with Chronic Lymphocytic Leukaemia (CLL) ­ A Multicenter Study of the CLL Research Consortium James et al #291 *Day 8 R325mg/m2 R375mg/m2 R 50mg/m2 R375mg/m2 R375mg/m2 R375mg/m2 R375mg/m2 R375mg/m2 Len 2.5mg/d Len 5mg/d D31 D33 D1 D8 D15 D21 D1 Len 10mg/d D29 Cycle 2 28 days Cycles 3 - 7 28 days Cycle 1 35 days • Standard pre-meds given and GCSF as per guidance • The study has closed to accrual with 69 treatment naive pts enrolled • 40 pts enrolled into arm A (< 65 yrs) • 27 in arm B (≥ 65 yrs) • 57 now have final response data • Primary Endpoint: Complete Response Phase II, 2 stage study * Increased lenalidomide dose to 5mg at day 8 or cycle 2

  34. Summary of results • 27/39 pts in arm A achieved a median L dose of 10 mg while only 13/27 pts in arm B tolerated the 10 mg L dose • Neutropenia was frequently Gr 3/4 in severity. • Gr3/4 AEs were reported in 72% of arm A pts and 82% of pts on arm B (p = 0.55) • Non-haem Gr3/4 toxicities reported in 37% of arm A and 52% of arm B (p = 0.31) • Older patients less likely to complete 7 cycles • Tumour flare more likely in younger patients

  35. Relevance to Practice • Strengths and Weaknesses • Open label, physician choice study with small numbers however a wide age range was used • No control: against single agent lenalidomide • Access to lenalidomide in this setting is currently via trials in the UK • Ideally recruitment to those trials should be encouraged rather than IFR requests for this regimen • There is a need to reinforce increased value of combination treatment vs single agent in CLL

  36. Lenalidomide and Rituximab for the Initial Treatment of Patients with Chronic Lymphocytic Leukaemia (CLL) James et al #291 Escalation of lenalidomide ONLY when no major toxicity seen 40% of pts <65 achieved 10mg dose escalation • n=69 • Cycle 1: • Lenalidomide (L): d1-7: 2.5mg, d8-21: 5mg, d22-35: no L • Rituximab (R): d29: 50mg/m² d31: 325mg/m² d33: 375mg/m² • Cycle 2: • L: d1-21: 5mg, d22-28: no L • R: d1, 8, 15, 22: 375mg/m² • Cycle 3: (28 days) Cycle 7 (28 days) • L: d1-21: 10mg, d22-28: no L • R: d1 375mg/m² • Allopurinol 300mg, aspirin 8mg

  37. Results and Relevance to Practice • Primary Endpoint: Complete Remission Rate: 16% • Secondary Endpoints: • Overall Response Rate: 88% • Progression Free Survival: 19-20 months • Active regime but lenalidomide is very toxic and requires intra patient dose increase • This is one to watch and could demonstrate better results as currently only 16% CR

  38. A Combination of Fludarabine/Rituximab with Escalating Doses of Lenalidomide in Previously Untreated Chronic Lymphocytic Leukaemia (CLL): The REVLIRIT CLL5 AGMT Phase I/II Study,  Egle et al #292 • n=45 • Cycle 1: • Fludarabine (F): d1-3: 40mg/m² oral • Lenalidomide (L): d1-6: 0mg, d7-21: 2.5mg, d22-28 0mg • Rituximab (R): d4 375mg/m² • Cycle 2: • F: d1-3: 40mg/m² oral • L: d1-21: 5mg, d22-28 no L • R: d1: 500mg/m² • Cycle 3: (28 days) Cycle 6 (28 days) • F: d1-3: 40mg/m² oral • L: d1-21: 10mg (then escalated by 5mg each cycle), d22-28:no L • R: d1 500mg/m²

  39. Results and Relevance to Practice • Primary Endpoint: MTD, not reached • 34% pts escalated to 25mg, 27% pts didn’t reach 10mg • Secondary Endpoint: • Complete Response: 49% • Partial Response: 38% • Another promising combination with good activity, (CR rate) again requiring intra patient dose escalation • Therefore risk of errors will be high • If this enters clinical practice, pharmacy can expect to be busy!

  40. Fractionated Doses of Gemtuzumab Ozogamicin (GO) Combined to Standard Chemotherapy (CT) Improve Event-Free and Overall Survival in Newly-Diagnosed De Novo AML Patients Aged 50-70 Years Old, Castaigne et al #6 • Prospective randomized phase 3 trial from the Acute Leukaemia French Association (ALFA) • 278 pts (50-70 yrs) with de novo AML: • Received DA with or without GO (3mg/m² on days 1, 4 and 7) (DA vs DAGO) • Primary endpoint: EFS • Secondary endpoint: RR, DFS, Safety and OS • Main additional toxicities in DAGO arm were prolonged G≥3 thrombocytopenia (n=19) and veno-occlusive disease (n=3)

  41. Relevance to Practice • The addition of GO to standard chemotherapy improved EFS and OS in elderly patients with AML and is well tolerated • Historically a difficult patient group to treat • Investigators used a different dosing schedule compared to that used in MRC trials • The drug has been recently, voluntarily withdrawn from the market – hopefully this will prompt reconsideration by Pfizer

  42. High Dose (HD-AraC) Vs Standard Dose Cytosine Arabinoside (SD-AraC) During Induction and IL-2 Vs Observation After Consolidation/Autologous Stem Cell Transplantation in Patients with Acute Myelogenous Leukaemia (AML), Willemze et al #257 Daunorubicin 50mg/m² for 3/7 Etoposide 50mg/m² for 5/7 HD AraC 3 g/m²/12hrsfor 4/7 n=973 Daunorubicin + AraC(500 mg/m²/12hrs for 6/7) All CR pts R Daunorubicin 50mg/m² for 3/7 Etoposide 50mg/m² for 5/7 SD AraC 100 mg/m²for 10/7 n=969 • Final report of the AML-12 trial of EORTC and GIMEMA Leukaemia Groups • Randomised phase III trial of 2005 newly diagnosed AML patients from 68 centres • Median age 45yrs (15 – 50 yrs) • >30% blasts • Excluded APL, pts converting from MDS/MPD and CML to AML

  43. Summary of Results • Median F/U: 6yrs • At 6yrs 1114 pts had died • Primary Endpoint: • OS at 6yrs: 42.5% (HD AraC) vs 38.7% (SD AraC) non sig • OS in pts <45yrs: 51.9% vs 43.4% (p=0.009) • Secondary Endpoints: • CR: 78.7% (HD AraC) vs 71.9% (SD AraC) (p=0.002) • PFS at 6yrs in pts <45yrs: 52.8% vs 46.6% non sig • Toxicity: no significant difference in rates of death • Good sample size that met statistical requirements • However the standard comparator is not equivalent to UK practice

  44. Relevance to Practice High Dose AraC has significant benefit compared to Standard Dose AraC for AML induction, but only in patients under 45 years This is relevant for the UK, however we may need to put this into context with UK gold standard therapy UK trial portfolio is looking at development/integration of newer agents in consolidation

  45. Activity of Bosutinib by Baseline and Emergent Mutation Status in Philadelphia Chromosome–Positive Leukaemia Patients with Resistance or Intolerance to Other Tyrosine Kinase Inhibitors, Khoury et al #110 Phase I/II trial in Ph+ leukaemias following intolerance to imatinib plus a second generation TKI (dasatinib/nilotinib) CHR rates were generally similar across the arms however lower response rates were seen in dasatinib resistant mutations Emergent mutations on treatment were mostly T315I or dasatinib predictable mutations Bosutinib shows poor activity in T315I patients Another TKI, good or bad thing?

  46. MyELOMA

  47. Maintenance Therapy with Bortezomib Plus Thalidomide (VT) or Bortezomib Plus Prednisone (VP) In Elderly Myeloma Patients Included In the GEM2005MAS65 Spanish Randomized Trial Mateos et al #477 • 2 stage, randomised trial including 260 elderly untreated myeloma patients. Maintenance regimen • Stage 1: VMP and VTP as induction yielded similar Overall Response Rates of 80% and 81% respectively (Mateos et al Lancet Oncology 2010) • Bortezomib 1.3mg/m2 iv on days 1, 4, 8 and 11 at 3 month intervals and • Prednisone 50mg po alt day or • Thalidomide 50mg po OD

  48. Summary of results • 178 pts analysed – remaining relapsed before maintenance • Median follow-up after second randomization 34 months (8-54) • Overall, maintenance therapy resulted in an increased IF-CR rate, from 24% after induction up to 42% with maintenance • Better depth of response • For all patients receiving maintenance therapy, • Median PFS from initiation of treatment was 35 months (95% CI 29-39) • Median OS 60 months (95% CI 51-69) • From the randomization to maintenance therapy, • Median PFS 30 months (95% CI 21–39) vs. 24 months (95% CI 15–33; p=0·1) for VT vs. VP respectively • No significant difference in overall survival from this time point for VT and VP arms were observed (HR 1·4, 95% CI 0·8–2·4)

  49. Adverse event profile • Only 6% discontinued due to toxicity • ≥Grade 3 haematological toxicity: • neutropenia in one patient in each arm • Most non-haematological toxicity was grade 1-2 in both arms • Incidence was greater for VT as compared with VP arm (p=0·0001). • Seven patients in VT arm developed cardiac events vs. one patient in the VP arm • Gastrointestinal toxicity, as constipation or paralitic ileus, was reported in 11 patients in VT and 3 patients in VP arm. • Grade 3-4 peripheral neuropathy was observed in 9 patients in VT (1 new, 8 worsened) and 3 in VP arm.

  50. Relevance to Practice • Strengths and Weaknesses • 1/3rd of patients didn’t reach maintenance • Interesting that there is no difference between induction regimens or maintenance • This could be an option instead of maintenance lenalidomide • Velcade only every 3 months • Can avoid ImID use (use at relapse) • Much cheaper than lenalidomide (1 yr Tx = 4 mo lenalidomide) • Reduced clinic appointments • Needs a phase 3 study to support clinical use