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Previously Treated Multiple Myeloma

///Previously Treated Multiple Myeloma

Haematological cancer: Where are we now with the treatment of multiple myeloma?

Altmetric: 5More detail Article | OPEN Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing

Trails and Tribulations

Not all who wander are lost…I have seen this a lot lately, adorning the shirts and walls amongst varied communities—from artists to drifters to star-seeking entrepreneurs to anyone who just likes the idea of following an unbeaten path.

While there is nothing wrong with a good quote that inspires you to one day seek adventure as a fearless trailblazer wandering bold new paths in life that in 4 easy steps can help change the world, I have to say that training for a 100 mile bike race during one of the hottest days in July is just not one of those times.

A couple of weekends ago, Faith, Brian, Niels, and I headed out to log some training time as we prepare for the Big Dam Bridge 100 coming up in September. Even early in the day it was hot. Back in the UK they called it a heat wave just last month when the temps peaked at about 30° C, which 86° F. Here in Little Rock, that’s a cold snap. The weather in the south is nothing short of diverse: Hurricanes, tornadoes, floods, droughts, ice, snow, and of course, the heat, which was close to triple digits that day.

Anyway, so despite the extreme heat, we logged roughly 50 miles, which should have been less, but I will get to that in a moment. I’ve been using this Strava app, which tracks key stats like distance, pace, speed, and even compares how I am doing over time. It’s actually pretty cool. You can see our cycling route in orange on the map image taken from the app.

I’m sure you have already noticed the straight line there with no outlet. So, in the age where GPS navigation is literally at your fingertips, one might say it would be difficult to make a wrong turn while out on the cycling trails. I mean it is pretty rare, unless of course you stop at a bar along the way, which we didn’t (not this time anyway).

I’m not complaining, it’s our own fault that we failed to properly follow the intended route. Well, let me say it another way… it’s our own fault we improperly followed Niels down the road to nowhere.
After a few short minutes of riding along, having seen no cars and no passers-by, I became quite confident that this was indeed a bad decision.

$*&%! Niels.

That’s when I first noticed the old man at the edge of his property, rocking in a creepy rhythm in his ratty chair. I’m pretty sure he was armed. Maybe it was the rusty sign halfway tacked up to a tree that read: PRIVATE PROPERTY. IF YOU CAN READ THIS YOU ARE IN RANGE that lead me to that assumption. The Old Man (as commonly referred to over the last couple of weeks) stiffened when he saw us, the rocking chair tilting back on its feet. At this point I fully expected the next sound I heard to be that of him cocking his rifle.

I was a bit surprised when The Old Man nodded, took a sip of his coffee and half-smiled as we rode past him.

That’s probably whiskey.

Ignoring all signs we were not on the correct course, we continued on for a while longer… well, until we reached the end.

A dead end road. $*&%! Niels.

So we headed back, found our way onto the correct route, and finished the rest of the way home. I was exhausted and drenched in sweat.

Oh, by the way, Niels and Brian stopped and chatted with The Old Man, who actually didn’t have a gun and was quite personable. I’m pretty sure they are all getting together to have coffee next week.

Trails and Tribulations image

Subaru and Leukemia & Lymphoma Society Blanket Myeloma Institute with Love

Gareth Morgan, M.D., Ph.D., (third from left) poses with patients and staff at the Myeloma Institute who welcomed the donation of blankets.

Gareth Morgan, M.D., Ph.D., (third from left) poses with patients and staff at the Myeloma Institute who welcomed the donation of blankets.

Aug. 4, 2017 | Patients of the UAMS Myeloma Institute will soon be wrapped in additional care and comfort, thanks to the Subaru Loves to Care initiative launched last year by the vehicle manufacturer in partnership with the Leukemia & Lymphoma Society.

As part of the nationwide initiative, employees from the Subaru of Little Rock dealership and the Arkansas division of the Leukemia & Lymphoma Society arrived for a noon visit July 26 bearing boxes filled with nearly 100 blankets to share with patients receiving treatment in the Myeloma Institute’s fourth-floor infusion clinic.

“This is a really important gift for us and we thank you all very much,” Gareth Morgan, M.D., Ph.D., director of the Myeloma Institute, told those assembled for the presentation, including several patients and their families.

“With temperatures reaching nearly 100 degrees outside right now, I guess some may wonder why these patients are getting these blankets now,” Morgan said. “But if you’ve been in a hospital for any amount of time, you understand that it can get very cold in here,” he added with a chuckle.

Delivering the blankets to UAMS were Leigh Ann Brannon of the Leukemia & Lymphoma Society and Subaru of Little Rock’s Lucas Darius, Charles Clark and Cecil Turner, manager of marketing and sales. Turner said his own life had been touched by a loved one diagnosed with cancer.

More than 38,000 blankets will be delivered across the country to patients in their communities fighting cancer.

Some of the patients like Bennie Utley, of Cabot, have been battling the illness for years.

“I was diagnosed in 2005,” Utley said. “My urologist referred me here for another disease and my quality of life is really good. I am happy to have this place so close to us.”

Donald Robertson and his wife, Yolanda, began traveling from Baton Rouge, Louisiana, to Little Rock for his treatment after he was diagnosed three years ago.

“We wanted to come to the top place for stem-cell transplant,” said Yolanda.

This summer, visitors to 475 Subaru retailers nationwide were given the chance to share personalized messages of hope to patients in their local communities. Those participating also received a bracelet to help spread awareness of leukemia and lymphoma and the automaker’s goal to extend care and hope.

After distributing the blankets, the Leukemia & Lymphoma Society, which exists to find cures and ensure access to treatment for blood cancer patients, including those with myeloma, will feature online inspiring stories and photos of survivors and patients from across the nation.

The UAMS Myeloma Institute is the world’s foremost research and treatment center for multiple myeloma, a cancer of the blood’s plasma cells. Visit  Find us on FacebookTwitter or YouTube.

From the Director

Gareth Morgan, M.D., Ph.DDear Readers,

Quality of life for patients is a top priority at the Myeloma Institute.  Our team is committed to providing a comprehensive, holistic experience, including effective disease management and emotional support for patients, family members and caregivers. We believe that patients should be able to live their lives as fully as possible with minimal side effects from treatment.

Bone disease is a significant complication of myeloma that affects a majority of patients. In this issue we describe how we are exploring ways to combat bone disease and give patients improved, pain-free mobility. Our researchers, in collaboration with colleagues in other specialties, such as orthopaedics and radiology, are investigating the nuances of bone remodeling at the cellular level.

Also in this issue are two patient stories that attest to living life fully with a high quality of life. We are continually inspired by the perseverance and inner strength of our patients.

Our steadfast mission is to provide the highest level of comprehensive care for the best outcomes and optimal living, while researching new methods of targeted treatment that lead to cure.

Cheers and kind regards,

Gareth Morgan, M.D., Ph.D
Director, UAMS Myeloma Institute

Bone Disease in Myeloma

A: Large pelvic lesion prior to treatment B: Remineralization following multi-agent treatment with stem cell transplant

Donghoon Yoon, Ph.D., in his lab where his focus is on the factors and mechanisms of bone metabolism in myeloma

Bone disease is a hallmark of myeloma, affecting up to 90 percent of patients. An unexplained fracture or bone pain can be the first sign that something is not right and often leads patients to seek medical attention.

Bone lesions are present in about 70 percent of myeloma patients at diagnosis, with the most commonly involved sites being the skull, spine, rib cage and pelvis. Almost 50 percent of newly diagnosed patients will develop a fracture during the first year following diagnosis and about 65 percent of newly diagnosed patients will develop a fracture at some point during the course of their disease.

Like all human tissue, bone is continually changing — it is not static. In a healthy individual, there is a balance between destruction of old bone and development of new bone. That balance ensures that bones are strong, maintain proper density, and have the capacity to heal if injured. In patients with myeloma, the normal process of bone remodeling is off kilter. The rate of resorption of old cells outpaces production of new cells, resulting in a net loss of bone mass.

More specifically, osteoclasts continually resorb damaged bone, which is replaced by new bone made by osteoblasts. Either directly or through complex interactions with the bone marrow microenvironment, myeloma cells stimulate the bone resorptive activity of osteoclasts and suppress the bone-forming activity of osteoblasts.

As a result of altered bone remodeling, myeloma patients typically develop osteoporosis and lytic lesions — holes that give the affected bones a Swiss-cheese-type look — that can lead to painful fractures and related complications, including spinal cord compression and hypercalcemia (excess calcium in the blood that can cause confusion). Bone loss is often more prevalent at sites populated by myeloma cells and is more pronounced in older patients.

Compromised bone health can have devastating effects on a patient’s quality of life, said Maurizio Zangari, M.D., professor in the UAMS College of Medicine and director of bone disease research at the Myeloma Institute.

“Almost all of our patients are at increased risk for long bone fractures or vertebral collapse,” Zangari said. “We want to minimize further bone loss and stimulate bone growth so that patients can resume adequate mobility, and, in the case of vertebral lesions, we want to be able to prevent further collapse.”

Most myeloma patients at the institute, including those with no detectable bone lesions and those with myeloma-related osteopenia or osteoporosis, receive bisphosphonates — usually a monthly infusion of zoledronic acid (Zometa) — as a routine part of their treatment. Bisphosphonates inhibit osteoclasts and are effective at reducing the incidence of bone fractures. However, they can negatively affect the kidneys, so renal function must be closely monitored, especially in patients with established kidney problems. If a patient’s vitamin D level is low, a supplement might be indicated to support bone health and maximize the effectiveness of the bisphosphonate.

Assessment of bone disease is done via magnetic resonance imaging (MRI), bone density exams (DEXA) and positron emission tomography (PET) scans. The Myeloma Institute has a wealth of data from these tests conducted over many years. The data document bone disease progression and improvements based on specific treatments, which in turn help our doctors determine optimal treatments and the timing of treatments.

Proteasome inhibitors, such as bortezomib and carfilzomib, have proven effective for improving bone remodeling since they both inhibit bone resorption and promote bone formation. Zangari and Larry Suva, Ph.D., formerly with the Department of Orthopaedic Surgery in the UAMS College of Medicine, conducted a review of clinical studies focused on bone disease – “The effects of proteasome inhibitors on bone remodeling in multiple myeloma,” published in 2016 in the journal Bone.

The majority of those studies demonstrated that treatment with bortezomib (Velcade) is associated with an increase in the levels of biomarkers associated with bone formation, such as serum bone alkaline phosphatase, and a reduction in the levels of biomarkers associated with bone resorption. Similarly, carfilzomib has been shown to stimulate osteoblasts (bone-forming cells) in myeloma patients.

Of particular interest is the relationship between the anti-myeloma activity of proteasome inhibitors and the presence of serum parathyroid hormone (PTH). Zangari reported preliminary evidence indicating that high spiking levels of PTH in bone marrow are associated with better response to bortezomib treatment (“Parathyroid hormone receptor mediates the anti-myeloma effect of proteasome inhibitors,” published in 2014 in Bone). This information was also supported by gene arrays done on bone marrow biopsy specimens. Zangari and his research team are investigating the correlation between the PTH system and proteasome inhibitors, as the findings could shed light on potential targeted treatment strategies.

A more recent study by Zangari and colleagues, reported in “Extensive remineralization of large pelvic lytic lesions following total therapy treatment in patients with multiple myeloma,” published in February 2017 in Journal of Bone and Mineral Research, was initiated after observing unexpected radiological improvement in pelvic CT assessment in a Myeloma Institute patient treated in one of the institute’s total therapy protocols.

The patient presented with a pathological fracture of the acetabulum (the socket of the hipbone) and large lytic lesions in the pelvis. Following multi-agent treatment, including bortezomib, as part of the total therapy regimen, CT imaging revealed significant remineralization of the lesions.

Zangari’s retrospective analysis of 62 patients treated with combination therapy demonstrated a significant percentage — 43 percent — of remineralization of large pelvic lytic lesions. The data indicate that lytic lesions, at least in the pelvis, retain the capacity for remineralization, which bodes well for restoring patients’ activity levels.

“These findings are very positive and give us the basis for further research,” Zangari said.

When surgery is required, Zangari and other Myeloma Institute physicians call upon specialists at UAMS who understand the complexities of myeloma. Corey Montgomery, M.D., and Richard Nicholas, M.D., in the Department of Orthopaedic Surgery specialize in oncology. They see about 26 new myeloma referrals, resulting in about 20 procedures — mostly on the long bones — per year.  T. Glenn Pait, M.D., professor in the UAMS College of Medicine Departments of Neurosurgery and Orthopaedic Surgery, operates on the spine. He typically receives two referrals per week and performs spine surgery 20 times per year on myeloma patients. Vertebral collapse is treated by the UAMS interventional radiology team. The most common procedure for myeloma patients, kyphoplasty, involves the creation of space between vertebral bodies and injection of a filler to maintain the space.

“We are very fortunate to have such skilled experts who can provide surgical care for our patients,” Zangari said. “They help us improve patients’ quality of life, and they operate with both compassion and a keen understanding of the myeloma disease process.”

In addition to a current clinical trial (see page 8) Zangari anticipates future studies that focus on bone-forming agents, such as PTH, and the introduction of antibodies against sclerostin (a substance that inhibits bone resorption). “Our goals are to provide treatment based on a thorough understanding of bone disease processes and to give patients the best possible quality of life,” he said.