Thread by @rajshekharucms

Although a negative trial, the recently published Vorinostat-Len (VR) vs Len (R) analysis of Myeloma XI RCT had some important learning points🧵#mmsm @profghjackson @DrGarethMorgan1
tinyurl.com/ysxu446k

1. Drugs with high symptomatic toxicities are 𝒏𝒐𝒕 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 𝐜𝐞𝐧𝐬𝐨𝐫𝐞𝐝 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 about⬆️censoring in VR arm, but there wasn't.

3. Digressing a bit, but TOURMALINE-MM3 had imbalanced censoring between arms (⬆️w ixazomib). This raises❓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 rest👇🏾. IMO, we 𝐜𝐚𝐧𝐧𝐨𝐭 use this data to say the Seli may work better in del(17p).

6. Great to see 𝐏𝐅𝐒𝟐 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) 👇🏾. Kudos to BJH @BritSocHaem for publishing this negative RCT! #mmsm

Tagging lead authors @_DrCP and @JennerMatthew