From Tragedy to Triumph: How Thalidomide, the Most Notorious Drug of the 20th Century, Revolutionized Myeloma Treatment
➡️ A story of science, serendipity, and silent heroes.
🔹The Dark Beginning
Thalidomide was synthesized in 1954 and soon developed into a sleeping pill by German pharma company Chemie Grünenthal. Marketed across 40+ countries by the late 1950s, it was widely hailed as a safe alternative to barbiturates.
Then came disaster.
Used to treat morning sickness in early pregnancy, thalidomide caused phocomelia—a horrific birth defect involving shortened or absent limbs.
By 1961, ~10,000 babies were affected worldwide.
But in the US, tragedy was largely averted—thanks to Dr. Frances Kelsey, a new FDA reviewer who refused to approve the drug without sufficient evidence of safety.
🔗 Read more: Dr. Kelsey’s legacy – FDA
🔹Scientific Ripples
Out of catastrophe came stricter drug laws. For the first time, both safety and efficacy became FDA mandates.
Astute clinicians even then wondered—Could a drug toxic to developing limbs also affect rapidly dividing cancer cells?
Early 1960s trials (including by @MSKCancerCenter) tested thalidomide in cancers including myeloma, but saw no success.
🔹Hope Rekindled – Leprosy and Immunology
Thalidomide faded from cancer research—until it was given off-label to patients with erythema nodosum leprosum, a painful immune complication of leprosy.
The results were astounding.
🔹 Lesions healed in hours
🔹 TNF-alpha inhibition discovered
🔹 Used later in Behçet’s disease, HIV wasting, GVHD
But how it caused fetal damage remained mysterious.
Then came a radical new idea—angiogenesis.
Pioneered by Dr. Judah Folkman and Dr. Robert D’Amato, the concept that cancers require new blood vessels gave new life to thalidomide. They found it was anti-angiogenic—perhaps this explained both its teratogenicity and its anti-cancer potential.
🔹The Silent Catalyst: Dr. Leif Bergsagel
This is where the forgotten name deserves the spotlight:
🔸 Dr. Leif Bergsagel of @MayoClinic
In 1997, Dr. Bergsagel attended the International Society of Hematology meeting in Stockholm. There, Dr. Folkman presented his vision of anti-angiogenesis in cancer. Bergsagel was captivated.
Shortly after, Beth Jacobson, wife of a myeloma patient, contacted him for advice. He told her:
🗨️ “Contact Dr. Folkman. He’s testing something new—thalidomide.”
Jacobson did. She then suggested this therapy to Dr. Bart Barlogie at the University of Arkansas, her husband’s physician.
Barlogie was bold.
Despite his patient not responding, he pursued a compassionate IND for 3 patients.
One of them responded. Dramatically.
That single event changed myeloma therapy forever.
🔹A New Era of Thalidomide
In 1999, @NEJM published the landmark paper showing that thalidomide yielded a 25–30% response in patients with relapsed/refractory myeloma.
📄 Thalidomide in Multiple Myeloma – NEJM, 1999
The field exploded.
I led the first confirmatory trial and later, a randomized trial through @eaonc that led to FDA approval of thalidomide for myeloma.
📄 My JCO Study on Thalidomide
Then came safer, more effective analogs:
🧪 Lenalidomide (Revlimid)
🧪 Pomalidomide (Pomalyst)
The IMiD class (immunomodulatory drugs) was born—drastically extending survival for myeloma patients.
🔹Legacy & Lessons
🧬 Thalidomide revolutionized myeloma care not just through efficacy, but by bringing attention, investment, and innovation into a previously stagnant field.
🔍 How it works? Still not fully clear:
- TNF-α inhibition
- Anti-angiogenesis
- Free radical damage
- Cereblon binding (most accepted today)
🔗 Cereblon: The CRBN–IMiD Puzzle – Cell Reports
💡 Takeaways:
- Clinicians matter. They see what data cannot show.
- Serendipity exists, but only helps those who act on it.
- Patient advocacy saves lives.
- Science is not linear. This was a bedside → bench → bedside revolution.
🔹Unsung Hero of Thalidomide
This post is incomplete without acknowledging a key figure who rarely receives credit:
👉 Dr. Leif Bergsagel (@Leif_Bergsagel)
If he hadn’t guided Beth Jacobson to Dr. Folkman…
If he hadn’t made the link…
We may not have thalidomide, lenalidomide, or pomalidomide in myeloma today.
This thread aims to rectify that oversight.
🔗 Further Reading & References
- MAin source: Vincent Rajkumar https://x.com/VincentRK/status/1924189959507890635
- Forbes: The Rebirth of Thalidomide by @matthewherper
- STAT News: The Comeback Drug with a Dark Past
- Mayo Proceedings: Historical Review on Thalidomide in Myeloma
📌 If you work in oncology, hematology, or drug development, the thalidomide story isn’t just history—it’s a case study on courage, controversy, and clinical brilliance.
🧵Tweet to honor forgotten heroes like Dr. Bergsagel.
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