Raj Chakraborty Profile picture
Jan 21, 2023 โ€ข 9 tweets โ€ข 5 min read โ€ข Read on X
Although a negative trial, the recently published Vorinostat-Len (VR) vs Len (R) analysis of Myeloma XI RCT had some important learning points๐Ÿงต#mmsm @profghjackson @DrGarethMorgan1
tinyurl.com/ysxu446k
1. Drugs with high symptomatic toxicities are ๐’๐’๐’• good for maintenance therapy. IMO, drugs like selinexor and belantamab mafadotin are perhaps in the same league and unlikely to be successful in maintenance setting. 2x greater risk of Rx discontinuation in Vorinostat arm!!
2. Great to see that number of patients ๐œ๐ž๐ง๐ฌ๐จ๐ซ๐ž๐ at each time point provided in K/M curve! PFS, as an endpoint, is prone to differential censoring. Given higher symptomatic toxicity, I would be concerned aboutโฌ†๏ธcensoring in VR arm, but there wasn't.
3. Digressing a bit, but TOURMALINE-MM3 had imbalanced censoring between arms (โฌ†๏ธw ixazomib). This raisesโ“about the legitimacy of a measly 5 mo. PFS benefit with Ixa, especially given no OS benefit yet and a slew of negative RCTs lately. tinyurl.com/2am4mau8
4. To properly interpret subgroup effects, p-value for subgroup interaction/heterogeneity must be provided in the Forest Plots, as in this trial. Although some trends noted, no statistically significant subgroup interaction here.
5. For comparison, the Forest Plot for PFS in BOSTON trial did not show p-value for heterogeneity. Hence, we don't know whether a significant subgroup effect existed in pts. with del(17p) vs rest๐Ÿ‘‡๐Ÿพ. IMO, we ๐œ๐š๐ง๐ง๐จ๐ญ use this data to say the Seli may work better in del(17p).
6. Great to see ๐๐…๐’๐Ÿ as a key secondary endpoint reported in this report of Myeloma XI trial. Given OS takes a long time to read out, PFS2 may be a reasonable compromise in trials of earlier lines of Rx cc @ManniMD1
7. Finally, such a well-written discussion. Was a pleasure to read (excerpt below) ๐Ÿ‘‡๐Ÿพ. Kudos to BJH @BritSocHaem for publishing this negative RCT! #mmsm
Tagging lead authors @_DrCP and @JennerMatthew

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More from @rajshekharucms

Jan 17
Imp. paper by @VincentRK ๐‘’๐‘ก ๐‘Ž๐‘™ on mode of progression in a ๐ฆ๐จ๐๐ž๐ซ๐ง ๐œ๐จ๐ก๐จ๐ซ๐ญ of patients with smoldering #myeloma!

Helpful for initial discussion in patients with ๐‡๐ข๐ ๐ก-๐‘๐ข๐ฌ๐ค ๐’๐Œ๐Œ re. clinical trials vs active surveillance vs Len

1/4 tinyurl.com/4w4bmzen
Image
๐Ÿ”‘finding: 23/71 pts. (~๐Ÿ‘๐Ÿ%) with HR-SMM progressed to clinically significant MDEs (Bone Disease/Hypercalcemia/Renal Failure) at a median f/u of ~4 years!

In other words, >2/3rd of patients with HR-SMM did ๐ง๐จ๐ญ have clinically significant MDEs at progression!

2/4 Image
What about all MDEs (CRAB)?

At a median follow-up of ~4 years, 39/71 patients (~๐Ÿ“๐Ÿ“%) with HR-SMM on active surveillance progressed to CRAB! This is ๐ฌ๐ฎ๐›๐ฌ๐ญ๐š๐ง๐ญ๐ข๐š๐ฅ๐ฅ๐ฒ ๐ฅ๐จ๐ฐ๐ž๐ซ than 2-year risk of ~50% in pts with HR-SMM, as we quote using 20/2/20!

3/4
Read 5 tweets
Dec 23, 2023
Our study on outcomes with Dara-VCD in AL #Amyloidosis outside of clinical trials: What did we learn beyond ANDROMEDA?
@columbiacancer @CAMPamyloidosis
@SLentzsch @MurielFinkel @MathewMaurer @DivayaB
1. Hopefully, the days are gone when ~30% of pts with stage IIIa and ~60-70% of stage IIIb would unfortunately die by 1 year! We show that early mortality has โฌ‡๏ธed (can't explain solely by early diagnosis since >65% of our cohort were stage IIIa/b and median NT-proBNP of ~3300) Image
2. Despite a sicker population than ANDROMEDA and a higher clone burden in bone marrow, hematologic & organ responses comparable (or even superior)! Image
Read 6 tweets
Nov 30, 2023
Phase III GMMG ReLApsE Trial #ASH23: Is it the last nail in the coffin of salvage auto-transplant in relapsed #MultipleMyeloma?

Lets unpack in this short ๐Ÿงต (also, an important teaching point on prognostic vs predictive marker!)

tinyurl.com/2s36byjf
The prevailing dogma regarding salvage ASCT in #Myeloma is to offer to pts who had prolonged remission after ASCT1 (typically >3 yrs).

The assumption is that a long remission after ASCT1 would ๐ฉ๐ซ๐ž๐๐ข๐œ๐ญ forโฌ†๏ธbenefit from ASCT2 over std therapies!

Enter ReLapse Trial!
What was the design?

โœ…1:1 randomization to Rd re-inductionโžก๏ธASCTโžก๏ธR maint. vs Rd continuous until PD
โœ…R-refractory not allowed (only 11% R-exposed)
โœ…Only pts with time to PDโ‰ฅ12 mo. from ASCT1 allowed! Image
Read 7 tweets
Sep 29, 2023
Few thoughts on CANOVA trial (Ven-Dex vs Pom-Dex in t[11;14]). I do think that venetoclax still has a role in t(11;14) plasma cell disorders, but these results add nuance to my interpretation of venetoclax data and how I will use it.
First, PFS numerically higher with Ven but not statistically significant is disappointing!

But one thing to note here is the differential censoring (something I have learnt from @VPrasadMDMPH to always pay attention to in PFS curves):
7% (Ven) vs 20% (Pom) at 10 mo. Image
We can only speculate as to why, but from the TTNT curves, it seems to be because more patients in Pom-Dex arm switched to a subsequent line of therapy without progression! Perhaps due to suboptimal response? Image
Read 6 tweets
Sep 29, 2023
With high-risk #MultipleMyeloma being a challenging entity to manage despite new drugs, the ๐†๐Œ๐Œ๐†-๐‚๐Ž๐๐‚๐„๐๐“ ๐ฌ๐ญ๐ฎ๐๐ฒ #IMS23 @JCO_ASCO is an imp. addition! ๐Ÿงตon the key takeaways and what can we learn (with focus on ASCT-Eligible pts)
tinyurl.com/2rumue4e
First, lets look at the regimen for transplant-eligible pts:
Isa-KRD x 6 โžก๏ธAuto-Transplant (90% single auto) โžก๏ธIsa-KRD x 4 โžก๏ธIsa-KR x โ‰ˆ2 years

๐Ÿ‘๐Ÿฝfor allowing 1 cycle of therapy prior to enrollment & oligo-/non-secretory disease!
Second, how was "high-risk" defined for inclusion in this trial?
ISS II/III
๐€๐๐ƒ
1 or more of: t(4;14), t(14;16), del(17p), or amp(1q)

Approx. 1/3rd of pts were double/triple-hit (โ‰ฅ2 high-risk abnormalities)!
Read 12 tweets
Jul 13, 2023
Important paper by IMWG on management of patients with ๐Œ๐ฒ๐ž๐ฅ๐จ๐ฆ๐š ๐‚๐š๐ฌ๐ญ ๐๐ž๐ฉ๐ก๐ซ๐จ๐ฉ๐š๐ญ๐ก๐ฒ! A๐Ÿงตon imp. clinical pearls in this paper and how to apply in daily clinical practice:
https://t.co/Zna40yvbaYtinyurl.com/5xk8ec26
Image
We commonly get consulted by other specialties when M-protein or increased serum FLC ratio is discovered during workup of kidney injury.

This table provides a great framework on how to approach these situations! Image
In such situations, I look for two critical pieces of info:

โœ…How high is the involved FLC (iFLC)?
โœ…What does 24-hour UPEP/IFE show? Predominantly albuminuria or BJ proteinuria or mixed?
Read 11 tweets

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