In the world of myeloma, the 1960s were a pivotal era marked by groundbreaking innovations that would forever change the landscape of treatment and technology.

In this article, we'll dive into the transformative developments of that decade, shedding light on the pioneering advancements that continue to shape how we approach multiple myeloma today.

From the arrival of chemotherapy to the emergence of novel diagnostic tools, the 1960s laid the foundation for a brighter future in the battle against this complex blood cancer.

The Evolution of Myeloma Treatment: From Leeches to Urethane in the 1940s

In the early history of multiple myeloma treatment, unconventional remedies like rhubarb, leeches, and quinine were attempted.

However, a significant milestone came in 1947 when Urethane was introduced as the first intentional drug for multiple myeloma therapy, with Alwall pioneering its use. Urethane had severe side effects, including anorexia, nausea, vomiting, cytopenias, and hepatic damage.

Furthermore, subsequent clinical trials revealed its high carcinogenicity and overall ineffectiveness. Remarkably, a randomized controlled trial comparing Urethane to a placebo in 83 symptomatic multiple myeloma patients demonstrated a longer median overall survival in the placebo group, highlighting the drug's limitations.

Numerous other anticancer drugs were also tested on myeloma mouse models, but they proved largely ineffective in targeting myeloma cells. During this era, the median overall survival (OS) for myeloma patients remained at six months.

Revolutionizing Myeloma Diagnosis: The Emergence of Immunofixation in 1964

In 1964, Wilson introduced a significant advancement in myeloma diagnosis through a technique known as immunofixation or direct immunoelectrophoresis. This method proved instrumental in identifying monoclonal immunoglobulins in patients' serum and urine samples following initial screening with protein electrophoresis.

The essence of protein electrophoresis lies in separating proteins based on their distinct electrical charges, allowing them to migrate at varying rates. During this process, immunoglobulins typically migrate to the gamma region.

Notably, the presence of monoclonal immunoglobulins leads to a characteristic "M-spike" in the gamma region, a hallmark not observed in individuals without myeloma.

This innovative diagnostic approach became pivotal in detecting even small monoclonal light chains that might go unnoticed in conventional electrophoresis methods.

The Turning Point: Melphalan and Prednisone - Revolutionizing Myeloma Treatment in the early 1960s

In the early 1960s, a significant breakthrough in treating multiple myeloma emerged with melphalan and prednisone.

This therapeutic approach marked a turning point, extending the median overall survival of patients to an impressive 3-4 years. Melphalan, also known as Alkeran, was originally discovered in 1958 by Blokhin in Moscow amidst the backdrop of the Cold War.

The drug initially went to England, where Galton conducted the first clinical studies in Western Europe. Subsequently, in 1962, a young faculty member named Danny Bergsagel explored its potential at MD Anderson.

While melphalan's most common side effect is myelosuppression, particularly thrombocytopenia, it is generally well-tolerated by patients. This milestone in myeloma treatment revolutionized patient outcomes and laid the foundation for further medical advancements.

Enhancing Myeloma Survival: The Synergistic Impact of Melphalan and Prednisone in the Late 1960s

In the late 1960s, a significant development in multiple myeloma treatment occurred when prednisone was combined with melphalan.

This innovative combination therapy, consisting of oral melphalan and prednisone, yielded a remarkable increase in patient survival by an additional 6 months compared to melphalan used as a standalone treatment.

Notably, patients undergoing long-term prednisone therapy experienced pronounced bone thinning, often leading to compression fractures, commonly associated with multiple myeloma.

Despite this challenge, prednisone's synergistic effect in enhancing melphalan's therapeutic activity was undeniable. As a result, this combined treatment approach gained widespread acceptance as a pivotal strategy in managing multiple myeloma, significantly impacting many patients' disease courses.

A Brief Glimpse into the Future of Myeloma After the 1960s 

After discovering how effective melphalan induction was combined with a corticosteroid, the stem cell transplant added is currently an effective treatment for almost all myeloma patients, increasing their life expectancy and quality of life.

Now that bone thinning is manageable with bone strengtheners like zoledronic acid and denosumab, using melphalan as induction for stem cell transplant has become a safe therapy with promising results.   

Conclusion

Understanding the pivotal developments in myeloma care during the 1960s is crucial for patients and caregivers. Back then, unconventional treatments like rhubarb and Urethane were tried, but despite being the first purposeful myeloma drug, the latter had severe side effects and limited efficacy.

The introduction of immunofixation in 1964 revolutionized myeloma diagnosis. In the early 1960s, melphalan and prednisone significantly extended patient survival despite some bone-related challenges.

These advancements paved the way for more modern treatments, such as stem cell transplants, which have greatly improved myeloma patients' lives, emphasizing the enduring impact of historical breakthroughs on myeloma care today. 

Invitation to Attend the Healthtree 2.0 Launch Event on October 23

Myeloma innovation didn't stop in the 1960s, and it's not stopping today! HealthTree is excited about the myeloma innovation happening today that's accelerating toward a cure. You can be part of this acceleration and innovation! 

Join us for an exciting journey through the history of myeloma care and the launch of HealthTree 2.0, a revolutionary platform designed to empower myeloma patients and caregivers.

We invite you to participate in this momentous occasion and make it even more special by hosting a virtual watch party with your friends, family, or support group.

Let's come together to celebrate the progress we've made in myeloma treatment and explore the promising future that lies ahead.

Register for our virtual launch today! 

Register for the HT 2.0 Launch

References for the article: 

Thomas, A., Mailankody, S., Korde, N., Kristinsson, S. Y., Turesson, I., & Landgren, O. (2012). Second malignancies after multiple myeloma: From 1960s to 2010s. Blood, 119(12), 2731-2737. https://doi.org/10.1182/blood-2011-12-381426 

Ribatti, D. (2018). A historical perspective on milestones in multiple myeloma research. European Journal of Haematology, 100(3), 221-228. https://doi.org/10.1111/ejh.13003 

Thanks to our event sponsors, Bristol Myers Squibb, Amgen and Genentech, for making this event possible.