Vincent Rajkumar: How a patient with cancer came up with the idea for a randomized trial, and how listening to him saved a lot of lives

Vincent Rajkumar, Editor-in-Chief of the Blood Cancer Journal, shared on Twitter:

“I would like to share the story of how a patient with cancer came up with the idea for a randomized trial, and how listening to him saved a lot of lives.

In 2002, I had just completed a randomized trial with the notorious drug thalidomide for the cancer, multiple myeloma.

Thalidomide would later be FDA approved on the basis of this trial. As a young investigator I was thrilled with the success and eager for the next exciting trial testing fancy new regimens. But a patient with myeloma, Mike Katz, had other ideas.

Mike was on national patient advocacy committees. He had battled myeloma for years and knew all of the recent advances. More importantly he attended numerous patient support group meetings and had his finger on the pulse of what myeloma patients were going through.

Mike was also on the ECOG-ACRIN Cancer Research Group, the NCI myeloma committee and listened as we debated ideas for the next myeloma trial. While docs talked about creating ‘exciting’ combinations, Mike said, ‘Listen, what patients really want is freedom from the side effects of Dexamethasone.’

He said, ‘All these new drugs don’t help if patients cannot take them. You guys are giving too much Dexamethasone. And people are suffering.’ Dexamethasone was used in myeloma at high doses to kill the cancer cells. It was an important component of therapy. Mike disagreed.

‘You are giving Dexamethasone at a high dose on the basis that this is how it has always been done. Please run a trial and see if in the era of new drugs you still need such high doses of dexamethasone.’

Rafael Fonseca was there. And along with Dr. Greipp we were all skeptical.

But Mike was not going to give up. He insisted we do a randomized trial of high dose dexamethasone versus low dose dexamethasone. To us the idea seemed destined to fail. It seemed so boring. We had waited 40 years for new drugs and Mike wants us to test Dex dosing!

However, we respected Mike. We knew he was aware of what patients were going through. We saw 100-200 myeloma patients a year. He interacted with thousands. He was also leading meetings of support group leaders who were leading meetings with lots of other myeloma patients.

So we proceeded to convince the NCI and ECOG-ACRIN Cancer Research Group leadership that testing the optimal dose of dexamethasone was the most important publicly funded randomized trial.
Rafael Fonseca took the lead.

Long story short, the trial accrued faster than any other myeloma trial we had done in national cooperative groups ever! Deaths with high dose dexamethasone (control, standard of dare arm) were significantly higher than with low dose dexamethasone!

We had hypothesized that by using low dose dexamethasone we will have less toxicity and similar efficacy. Little did we know that just a change in Dex dose would save lots of lives: At one year 96% were alive with low dose Dex versus 87% with high dose standard of care Dex.

There were other benefits as expected. All serious side effects including blood clots were lower with low dose Dex. The Lenalidomide plus low dose dexamethasone (Rd) regimen was born. The little ‘d’ signifies low dose dex.

Rd is now the backbone of most myeloma regimens. The lower dose of Dex has allowed us to build many 3-4 drug combinations. We are indebted to Mike. We grieve his loss. His legacy and work with ECOG-ACRIN Cancer Research Group, ASCO, the NCI, NIH, International Myeloma Foundation endures.

ASCO honored Mike in 2014 with the Partners in Progress Award. He narrated this story when he accepted the Award at the ASCO Annual Meeting. See also.

Our randomized trial of high dose versus low dose dexamethasone was published in The Lancet Oncology and is one of the most cited myeloma papers ever with over 1000 citations. See article here.

Here is his son Jason sharing how his father’s story.”

Source: Vincent Rajkumar/Twitter/X