Multiple Myeloma updates from recent conferences:
1) Newly diagnosed myeloma trials showed improved progression-free and overall survival with carfilzomib/lenalidomide/dexamethasone induction followed by autologous stem cell transplant compared to standard therapies.
2) For relapsed myeloma, carfilzomib with dexamethasone had significantly longer progression-free survival compared to bortezomib with dexamethasone. Carfilzomib, lenalidomide, and dexamethasone also improved outcomes over lenalidomide and dexamethasone.
3) Several novel agents are being studied in early phase trials for relapsed myeloma
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Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
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The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
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6. Newly diagnosed MM
• Zimmerman et al (ASCO abs #8510)
• Phase II trial of Carfilzomib/lenalidomide/dex
(KRd) extended treatment
• KRd x 4 transplant CLD x 4 modified
KRd until cycle 18 lenalidomide maintenance
• Early outcomes:
– 88% with MRD-negative disease after cycle 8
– Median f/u of 9.7 months: 52/53 progression-free
“The results to date compare favorably to any
prior treatment of NDMM”
7. Newly diagnosed MM- transplant?
• Gay et al, EHA abs #S101
• Multicenter randomized phase 3 trial to compare ASCT
with conventional chemotherapy plus lenalidomide
• LD x 4 then tandem ASCT with melphalan 200 OR CRD
x 6
• N=389
• Median PFS was 42 months for MEL200-ASCT and 28
months for CRD (HR 0.67, 95% CI 0.48-0.93, P=0.014).
• The 4-year OS was 87% for MEL200-ASCT and 71% for
CRD (HR 0.51, 95% CI 0.28-0.93, P=0.028)
• Transplant toxicities were short-lived
8. Newly diagnosed MM
• Orchard et al, EHA Abs #P338
• Ranodmized phase 2 of of 90Y-labelled anti-
CD66 + melphalan 200 vs melphalan 200
alone
• Targets BM plasma cells for higher radiation
delivery
• Significant improvement in CR for patients in
Arm A compared to Arm B (50% vs 25%, odds
ratio [85% 1-sided CI]: 0.277 [0.102, 0.753]).
9. Newly diagnosed MM
• Straka et al, ASCO abs #8511
• Results from two phase III studies of bortezomib
(BTZ) consolidation vs observation (OBS) post-
transplant
• N=371
• Greater response of ≥ VGPR after BTZ consolidation
than OBS
• PFS was significantly improved by ~6 months
• No improvement in OS
• Possible most benefit for
– Pts in less than VGPR
– High risk cytogenetics
10.
11. Newly diagnosed MM
• Holstein et al, ASCO abs #8523
• Updated analysis of CALGB/ECOG/BMT CTN 100104:
Lenalidomide (Len) vs. placebo (PBO) for
maintenance post-auto transplant
• TTP is 53 mos for Len and 27 mos for PBO (hazard
ratio (HR):0.54 (p < 0.001)
• Median OS has not been reached for the Len arm and
is 76 mos for PBO (HR: 0.60, p = 0.001)
• SPM is higher for Len compared with PBO (p = 0.005)
• TTP and OS benefit with Len was observed regardless
of
• whether pts were in a complete response or not at
randomization and for thalidomide vs. Len induction
12. Newly diagnosed MM-transplant
ineligible
• Facon et al, ASCO abs #8524, updated EHA S105
• Update of FIRST trial
• SCT-ineligible NDMM pts, n=1623
• Randomized 1:1:1
– Continuous Rd (28-day cycles)
– Rd for 18 cycles (Rd18)
– MPT for 12 cycles (42-day cycles)
Rd Rd18 MPT
OS (months) 68.9 56.7 48.9
PFS2 (months) 42.9 40.0 35
HR Rd vs MPT + .75 (95% CI, 0.62-0.90)
13. Newly diagnosed MM (NDMM)
Induction
High dose
chemotherapy
+ ASCT
Maintenance
or
consolidation
+ maintenance
Consolidation/
maintenance
Relapse
Salvage
Car/len/
dex
Car/len/
dex
Y-anti CD66
Continuous Rd
Maint
len
Bortez
consol
15. Relapsed/refractory myeloma
• Dimopoulos et al, ASCO abs #8509 (ENDEAVOR study)
• Carfilzomib and dexamethasone (Kd) vs bortezomib and
dexamethasone (Vd)
• Stratification by prior treatment, ISS stage, prior lines of tx,
route of tx
• N= 929
• Kd: improvement in median PFS vs Vd (18.7 months [mo]
vs 9.4 mo; hazard ratio = 0.53; P< .0001)
• ORRs were 76.9% and 62.6% (P< .0001)
• OS data immature
• Kd had a favorable benefit-risk profile with similar AEs and
less PN
16. Relapsed/refractory myeloma
• Dimopoulos et al, ASCO abs #8525
• Update of ASPIRE trial
• Carfilzomib, lenalidomide, and dexamethasone
(KRd) vs lenalidomide and dexamethasone (Rd)
• Secondary analysis based on number of lines of
previous therapy
• KRd after first relapse:
– 1-year improvement in median PFS vs Rd
– 9-month improvement in median PFS vs Rd in pts with
≥ 2 prior lines of therapy,
This is a salvage regimen that can be used after several lines
of therapy.
17. Relapsed/refractory myeloma
• Jakubowiak, ASCO abs #8573
• Randomized phase II study of bortezomib
(Btz)/dexamethasone (dex) +/- elotuzumab
(Elo) (antibody against CS1 or SLAMF7)
• Median PFS was 9.7 mo (EBd) vs 6.9 mo (Bd)
(HR 0.71; 70% CI 0.58, 0.87; p = 0.08
• Early overall survival (OS): HR of 0.61 (70% CI
0.43, 0.85)
• Limited added toxicity of antibody therapy
18. Relapsed/refractory myeloma
• Lonial et al, NEJM August 2015
• ELOQUENT-2: A phase III, randomized study of
lenalidomide (Len)/dexamethasone (dex)
with/without elotuzumab (Elo)
• PFS: ELd 19.4 (16.6, 22.2) months, Ld 14.9
(12.1, 17.2) months (HR [95% CI] 0.70 [0.57,
0.85]; p = 0.0004
• ORR (95% CI) was 79% (74, 83) ELd, 66% (60,
71) Ld (p = 0.0002)
19. Relapsed/refractory myeloma
• San Miguel, ASCO abs #8526
• PANORAMA-1: Panobinostat plus bortezomib and
dexamethasone (improvement in PFS by 4 mo vs
PB/bortez/dex)
• Subanalysis of pts who received prior bortezomib
and IMiDs
• PFS PAN arm was 10.6 mo (95% CI, 7.6-13.8) vs 5.8
mo for PBO arm
• ORR 58.5% vs 41% (P = .0179)
• Similar safety profile
This regimen is likely useful after exposure to novel induction
regimens
20. Relapsed/refractory myeloma- single
arm studies
• CHAMPION-1, a phase I/II study of weekly
carfilzomib/ dexamethasone (Berenson et al, ASCO
abs #8527)
– ORR 72%
– Clinical benefit rate 80%
– PFS 10.6 months
• Phase II study of panobinostat/lenalidomide/
weekly dexamethasone (Chari et al, ASCO abs
#8528)
– ORR of 45%,
– CBR of 85 %
– PFS of 7.5 mo
21. Relapsed/refractory myeloma- single
arm studies
• A phase I/II trial of very low to low-dose continuous
azacitidine +Len/dex
– Twelve pts achieved > MR, 9 > PR (3 VGPR) ]
– 30% clinical benefit response (CBR) and 22.5% response
rates.
– Responses lasted between 3 months and 2 years
• Phase II study of daratumumab (DARA)
monotherapy (Lonial et al, ASCO abs #LBA8512)
– ORR 29.2%, with 3 sCR, 10 VGPR, and 18 PR
– 7.4 month median duration of response
– Median TTP 3.7 months
– Median OS has not been reached
– Estimated 1-year OS rate is 65%.
22. Relapsed/refractory myeloma- single
arm studies
• Berenson et al, ASCO abs #8591
• Pomalidomide (POM), dexamethasone (DEX),
and pegylated liposomal doxorubicin (PLD)
• N= 46
• ORR 35%
• clinical benefit rate 47%
• PFS 5.23 mo
• Main AE’s: cytopenias
23. Relapse options
• Carfilzomib and dexamethasone
• Carfilzomib, lenalidomide, and
dexamethasone
• Bortezomib/dexamethasone /elotuzumab
• Lenalidomide /dexamethasone /elotuzumab
• Panobinostat plus bortezomib
• Pomalidomide/dex
