Noopur Raje, MD: Breaking the Mold to Improve Multiple Myeloma Treatment

A decade ago, most cancer researchers were thinking broadly about cancer. Many were focused on the tumor. In the field of multiple myeloma, a cancer of the blood’s plasma cells, few researchers were looking at the variety of cells that make up the bone marrow microenvironment.

When Dr. Noopur Raje arrived at the Mass General cancer center, she had the idea to build the lab focused solely on understanding the growth of multiple myeloma and finding better treatments. This concept was pretty unique and required Dr. Raje to persevere and work hard to build a successful research program. She believes that understanding how myeloma cells interact with their surrounding environment and the mechanics of the bone marrow microenvironment could be the key to shutting down myeloma growth, and may even be the pathway toward a cure.

As director of the center for multiple myeloma in the Mass General Cancer Center, Noopur is working to find new targets for clinical trials and to translate them into therapies that will improve the lives of her patients.

Welcome, Noopur.

A:  Thank you, Amy.

Q:  So I know you’ve said when you came to the Mass General Cancer Center that you really wanted to work with a focus on myeloma. I'm wondering if we can start there and talk about what you did and how you went about building the lab?

A:  I came to MGH in 2005 to start up a program. My intent was always to start up a multiple myeloma program and part of wanting to do that was after I’d been through residency at MGH, I knew there was a need for this in terms of clinical need for our patients. Because at that time, we were thinking about cancer more broadly. We were thinking about disease areas, but not necessarily so focused on a very small niche area, which multiple myeloma at that time was certainly a very niche area.

I also wanted to work in the lab. And again at that time, 2005, was about the time when genomics was big. We all were thinking about cancer more from a molecular standpoint. And most of us wanted to think about not so much what kind of cancer you had, but to really hone in and focus on if you had a molecular target, it didn’t matter where the cancer came from. We were going to attack that cancer in a more generic manner by targeting those specific genes which are causing that problem.

So, typically at MGH we did not have, labs which were focused on doing very disease-specific research. So, as far as the clinical piece was concerned, I think people absolutely welcomed us starting up a disease program which was focused on the space. The lab I did get-- it’s not so much pushback, but people were--“You know, this is not something which we typically do at MGH,” kind of an attitude. “So try it, see if it works.”

And I said, “Yeah, I am going to do it.” Because before doing my residency I’d worked across town at Dana Farber. I’d focused on multiple myeloma even before starting out with my residency. And this was a time, when we had all of these wonderful new drugs for multiple myeloma which absolutely did not exist before then.

We had two drugs for the last 50 years, and typically patients with multiple myeloma survived for two or three years. And this was the beginning of a real shift in how we were going to begin to think about the disease, how we were going to begin to take care of our patients with this disease.

And in addition to what we were going to be doing in the clinic, I really wanted to continue to do my work in the lab as well so it could inform what we did for our patients going forward. So, certainly there was skepticism, I would say. But I think as we've gone on, people have come around. I don't think there's that many focused labs, even today, disease-focused.

Q:  I'm surprised to hear you say there aren't very many labs that are disease-specific. Is there a reason for that?

A: You know, in the lab you think about biology more broadly. And there are lots of labs here and lots of good work coming out of these labs. But they're more driven around the biology which drives cancer and the biology can be extrapolated from one tumor type to a different tumor type.

In terms of what's happening in oncology right now, we are at a place where translational research is becoming a really important part of what we do. The targets that we are identifying in the lab are now becoming drugs, and these are actually making a big difference to our patients.

So now the labs are more focused. So we have our lung cancer group here is absolutely amazing, and they’ve done unbelievable work when it comes to targeted therapies. And we have the Termeer Cancer Center now which focuses on phase 1 first in human sort of these targeted approaches. So from a lab standpoint, people are going back somewhat to more disease-specific models. But in general, people are studying the biology of cancer, and I think my lab may be one of the few, even today in the cancer center, which is solely focused on myeloma.

Q:  And do you anticipate that things you're learning about myeloma will then be translated to other cancers or other illnesses?

A:  For sure. We've learned a lot from other cancers, which we apply to myeloma, and it goes both ways. I think what we've learned with myeloma in terms of understanding the biology of myelomas, the biology of the tumor cells, in relation to what surrounds those cancer cells, has really informed the field of oncology at large.

You know, we've always talked about myeloma being a very microenvironment-dependent cancer, so that it really has to rely on some of the surrounding cells for it to grow, for it to survive. And unless and until we target some of these other accessory cells, sure you can control the tumor, but not necessarily control it long enough.

So multiple myeloma is an example of a cancer which first has demonstrated the importance of the surrounding cells.

What you see today happening in oncology is we are certainly targeting tumor, but we are certainly targeting other cells, like the immune cells for example. We are constantly using drugs like the checkpoint inhibitors in the context of cancers. So we're not targeting the cancer, but we are waking up the immune system to try and target the cancer.

Q:  If you go back to when you were starting your lab and you mentioned there was some skepticism, how did you respond to that? Were there things that you did to kind of get people onto your side?

A:  You know, I think the most important thing is put your head down and do the work and then the work speaks for itself. I think the beauty of MGH is the people at MGH are incredible, so whatever you think of, you can actually do, because you can put resources behind it.

And the other beauty of MGH is it being a city-based hospital, you have patients who come from all over. So in terms of patients, we were able to build up a clinical practice pretty quickly. And because of the work which I do in my lab, that being very translational, the first thing we did set up was a tissue bank, and I can't tell you how patients are such an integral part of the research we do.

To date, Amy, I've never had a patient tell me, “No, you can't use my sample for research.” They are incredibly giving in terms of allowing us to understand the disease. And if we didn't have that ability to study their tumor specifically, we wouldn’t have been where we are.

Part of what I do in the lab is try and understand bones, because multiple myeloma is a bone marrow cancer. But one of the biggest problems with patients with multiple myeloma is that they can develop pretty aggressive bone disease. And simplistically put, it’s kind of an extreme form of osteoporosis.

So patients with myeloma can have thinning of their bones to the extent of fractures. And this can be quite debilitating. It can cause a lot of morbidity. And understanding why that happens and what are the factors which promote this kind of impact on the bones was quite important to us. And we started doing that in the lab. Along the way, we've tried to identify different drug targets to see if we can make things better. And we've been able to identify certain factors in the lab. So, I think end of the day, it was just being persistent and pushing ahead and doing what I really believed in doing.

I really enjoy taking care of patients and I've seen myeloma. I've been doing this now for more than 15 years. And I've seen what it was like before these drugs were available. And to me, the excitement was the drugs that we have today, they call bortezomib, carfilzomib, I've worked with them in the lab when they were called numbers. It was PS341, it did not have a name.

And we've seen them go from these drugs with numbers and letters to FDA approval. And when I started out, I told you that patients live for two and three years. On an average now, patients live for close to ten years or longer. So that's a big deal.

But at the same time, we haven’t cured the disease and that's why the only way to push ahead and try and get to the point where we can cure a majority of people is really trying to understand the biology. And that's what pushes me to keep doing what I'm doing.

Q:  You started along this path. You're doing something a little against the grain. I imagine it was a little nerve wracking, a little scary in the beginning. Was there a point when you knew this is working or we're doing it?

A:  So if I go to a few years back, when I started out, I did not want to start my lab right away. I wanted to focus only on the clinic, develop the clinic and then move the lab. It’s just so happened that as I was a year into developing the clinical program, I had this opportunity and we were able to get some funding. And I said, “Okay, we’ll do the lab.”

So it was two years ahead of when I had planned it. And it was tough initially because you were trying to juggle two things. I was doing something which I wanted to do a year or two down the line. But it was a little bit of a risk at that time, but it was an opportunity. Sometimes, you just have to get in there and do it because the stars are never going to align based on your plan. And you have to be able to move and do things. Lot of times, you know, I've early on questioned myself. Will I be able to continue to fund the lab? And that was critically important. I still think about that. You know, we’ve worked and we've been fortunate and we've really been blessed to have funding in place. And so far, we've continued to keep going.

Q:  What do you do when you have those moments of self doubt, of “Will this work? Can I do it?”

A:  You know, most times you have a lot of different things going on; it’s not just one thing. And I do think you do have to be willing to take a risk. You do have to be willing to know that things are not going to work, because everything doesn’t work the way you want it to work. And I think it’s really important to recognize when things are not going to work and say, “I've got to stop this.” Because you can go in completely blind to what you're doing.

I will tell you, when I started off my research and there's so much work we put into what we do, there's literally 10 or 15% of that which we publish. So there's a lot of work which we thought was a brilliant idea, which turns out to be not so. And I think recognizing that comes with age. As we get older, we say okay, enough is enough and I need to move on to the next thing.

And I think really listening and understanding helps. I've always along the way had a bunch of people who I use as my sounding boards. And those have been incredibly helpful to me in telling me when I'm being a complete idiot and saying, “Move on.”

And I think using those as resources, to me, has been really helpful.

Q:  And how did you find those people?

A:  So some of them are your work, your mentors, your colleagues. Some of them is family. My husband, and I will say my kids are now grown and I think as a family we are probably the toughest on each other. and I think listening to everybody helps.

You know, the other thing is being open-minded. You can't do everything. And you don’t know everything. And the more you understand and appreciate that, I think you have less of a problem reaching out. So I have no problem reaching out to people and saying, “Hey, I don’t understand this. Can you help me figure this out?”

And I think the beauty of being in a place like MGH is you can reach out. You can reach out to colleagues, you can reach out to your mentors, you can reach out to your mentees.

And I remember learning this, I did my internship, I had to do it again because I have actually trained back in India. But when I came here, the first thing as an intern, you're given a coat, just a short coat. It’s the MGH coat. And everybody at MGH right from the attending to the intern wears a short coat. And I said, “This is strange. But why does everybody--“

And I think my attending at the time told me, “You know, we learn from each other. We learn from the medical student and we learn from the attending and it goes both ways.” And that stuck in my mind forever. And to date, if I wear a white coat, I have only short white coats and that's been something I've tried to be true to.

Q: I'm curious, you mentioned you studied and trained in India, then came here. Do you think that gave you a different perspective when started over in essence when you got here?

A:  Right, so absolutely. I think seeing-- I did all my medical school training back in India. I had done my residency, I’d done a little on oncology. Not just India, and then I was in the U.K. for a couple of years. So in terms of why myeloma, I was fairly differentiated because I had done a lot of myeloma. But that did give me a lot of perspective. You know, it was hard and people always ask me this, “How was it for you to retrain again when you'd already done your training?”

And I think about this a lot, and I do think it would have been hard for me to retrain if I was at a place other than a place like this. To me, those residency years were incredible, because I met some of the smartest people around. And it was a completely different system. And learning from that completely different system  was so important to me. And I really enjoyed my residency years, actually.

But training in India, then looking at healthcare in the U.K. and then coming here obviously gives me a totally different perspective on how I approach medicine, how I take care of my patients. And generally, I think it just broadens your ability to put things into perspective, I would say.

Q:  Yeah. The openness, I think for me having lived and traveled other places and seen different ways of doing and being and seeing has such an impact.

A:  For sure. Traveling opens up people’s minds, seeing, experiencing different cultures. Working in the lab is really different from working in the clinic because even in my lab right now, I have people from all over the world. I have people from Italy, people from Japan, China and India. So, culturally, we become a lot more open to ideas, because you've grown up with a different set of rules depending on which part of the world you come from. So that lab experience actually helps build that up hugely.

Q:  How do you bring the people in your lab together to collaborate?

A:  Big believer of team. As a physician I think most physicians believe in team. You cannot do anything without collaboration and without being open-minded. And I think that same culture I bring back to the lab. So I have five people working the lab and all of them have their projects. But end of the day, I really believe it’s a family and we've got to help each other out and we've got to look out for each other. And there are times in research where things can be depressing, where one postdoc is doing really well, the other’s research is not going so well. We meet as a group, we are pretty close knit, and to me everybody’s a part of every project.

You know, it's a small lab so I can do that. But really being intellectually engaged in other people’s projects so that you're not siloed in your own little space, again, allows you to think more broadly. And this is where I do think it’s really important to be fairly open-minded. There are times in research when we can go down such a narrow path wherein you get so wedded to that idea that you can't see it any other way.

And that's why having your lab colleagues, speak up and tell you, “Hey, can you do it a different way?” And that's something which we've always tried to maintain in the lab. Because I do think medicine, research, is a team sport. It has to be done with collaboration.

And the other thing, like I said, is you can't do everything and you do not have to be good at everything, right? But if you are good at something, you can always use your colleague who’s better at something else, and work together and you're going to end up with something even better.

Q: I think it’s easy to feel that pressure, that you have to be the one to do all of the things. Is that something you think you learned over time, that it’s okay to specialize?

A:  I've come-- I think evolved. Because when I first started out, I wanted to be a physician. I loved internal medicine, and I didn't want to focus and do something narrow. And I was very against research. That was me. And I said, “I'm going to be taking care of patients, and that's it.”

And then as I did more and more, and as I saw more patients and then started thinking about them, to me research has become so important. So I never thought I would enter a lab before, but now I feel like I'm a lab geek. And really, that is sort of my happy zone.

Q: I love hearing about this balance in the relationship between your lab work and your patient work. How do you maintain that connection to make sure that it’s a sort of through line of everything that you're doing?

A:  So the work we do in the lab is very translational. There's a point about we work with patient samples, we are looking at targets. And a lot of what we've done in the lab is actually translated to what we've done in the clinic. So that what we found in the lab, we've actually done a phase one trial. What we've done with bone disease, we've gotten an FDA-approved drug now called denosumab. So the lab has informed what's happened in the clinic and vice versa.

The only way we could have done that was by focusing on this niche area. It’s allowed me to think about this disease from literally it’s biology to all the way to treatment. And that's something which has helped me. It’s kept the lab going. Even with my post docs in the lab who have done a PhD and haven’t had patient contact. I will bring them to my clinic so that they know the relevance of what they're doing. I love my patients. I think they're a very important part of my life. And what I do is driven by what they are going through. And I really try to bring that back to the lab so that my post docs understand that as well. To me, when a patient gives me a bone marrow sample to use in my lab, you know, that needs to be handled with the utmost respect.

You know, I do think we've been lucky with our disease because of all the different drugs we've had. Honestly, about ten FDA approvals in the last ten years in myeloma. So it’s been really an amazing drug development journey that we've been on. And we actually see that happen in real time with people, has been the most incredible experience.

Q:  Yeah, I can only imagine. How do you go about building relationships with your patients and with their families when they're in the midst of stressful, scary time?

A:  It’s tough, and cancer comes without any warning. And I think most of us are impacted by cancer, right? And my dad, who has been such an important force in my life for the person I am today, passed away from pancreatic cancer.

But understanding cancer from a family perspective. Understanding it from what my dad went through has really, I hope, made me a better oncologist, a better doctor. Understanding what a family goes through, because it’s not just the patient. We do focus a lot on the patient, but it’s the caregivers and it’s a process for the whole family. And just allowing ourselves to understand that is really, really important.

I will tell you that even today, if you never get used to having to share bad news with a family, and I always tell everybody who works with me, you should not get used to this. Because the day that I feel I've gotten used to sharing things with patients saying, “Hey, your disease has come back. Or, I'm putting you on hospice,” or my patient passes away, that's the day that I promise you I am going to retire.

Because, you know, it should not get any easier because that's what keeps you doing what you keep doing. And keeps you wanting to do the best by your patients.

They have tremendous trust in you. They come to you with a lot of hope. My patients, I tell them, they are my extended family and the other thing is they’ve been with me for years, and they do become a part of your lives. And it’s just not the patient, but it’s the family, the kids, the grandkids.

It's a privilege, really, being in medicine, being able to take care of them and being a part of their lives. And it just has to bring out the best in you.

Q:  Are there particular patients who have inspired you or who have really stayed with you over time?

A:  All my patients have been with me, and to me everybody’s different in different ways. So I'm different with different patients. And I love them all. They have this tremendous resilience. And it’s not one specific person, but it’s different people doing different things. And it’s how they handle life when they have been dealt all kinds of adversity, which helps you kind of wake up in the morning and say, “Hey, you've got to be able to do better than what you're doing.”

The one thing I always tell them is they can't be in this alone. It’s too much of a burden. And what I do try and tell them is we are going to do this together. It’s a journey, and we don’t know the answers. We don’t know what's going to happen tomorrow. But the most important thing is to have a trusting relationship, be transparent along the way. Because it’s really hard, specifically with a disease like ours, where I will say that this is an incurable cancer. But there's so much hope.

And so there's a lot of unknown there. And the unknown is for me as well as for the patient.

So building up that relationship is really important. And to me, I feel really lucky that I've been able to have these kinds of relationships with my patients. They’ve been incredible. They are my source of strength.

Q:  I'm wondering, were there things you learned in the experience with your father that changed your day-to-day practice?

A:  The hopefulness of my father. He had pancreatic cancer, and when I first learned about it, I was looking at the scans and I was sitting down with my colleagues looking at it. And I went back home and I told my dad, I said, “Dad, you've picked the worst.” I'm an oncologist, but pancreatic cancer, there's not a lot we can do. And this was now six years back.

And I was scared, and at the time, you're the only physician in the family, so everybody’s looking to you to give them the best case scenario.

I sat my dad down and I said, “Hey Dad, this is not good news. Pancreatic cancer can go horribly wrong quickly.”But my dad was the eternal optimist. He said, “It’s okay.” He was inoperable at the time.

I said, “We're going to try things, one thing at a time.” And what I learned from him was his resilience and his hopefulness. And never a day when he complained. And whenever I talked to him, “How are you feeling, Dad?” “Better, better, no poorer.” I said, “Okay, Dad.”

And he lived for, I think, a year and a half which is unheard of with metastatic pancreatic cancer. And I think it’s so important to give people hope. Be realistic, tell them, but at the same time be hopeful because you can't go through life without hope.

Q:  I want to ask you a little more about something you said earlier about not getting used to delivering bad news. What do you do to prepare to have those conversations? I imagine they're not easy to have.

A:  So, I like a lot of quiet time, actually. I come into work early. I like to have my cup of coffee without anybody there. My first hour is like my sacred hour, that's my thinking time. I don’t take elevators, I take stairs all the time. And that just gives me thinking time. It gives me active, but it gives me a lot of thinking time.

So before I go into a room, I have to have a little bit of time to myself to just think about it. I don’t call it meditation, but I just want a little bit of alone time to think it through and then go talk to the person. And then disconnecting from what I've done before. You know, life can get hectic, it’s busy. You're doing one thing after another. You're going from one patient’s room to another. And then you're going from meeting to next meeting. And I think a little bit of downtime is really important. And it’s just to kind of charge your batteries, reframe your own mindset a little bit before going in.

Q:  Really being present in each particular moment as it’s happening?

A:  Being with the patient, it’s so important, you know. And this is something we don’t appreciate enough as physician.

I am never on the computer, I'm with the patient. My notes take longer, I will do them the next day, but I don't care.

But being present in that moment is so important. And giving that person undivided attention is so important. And not turning your back and typing up what's going on with the patient because that can come later. So simple things like that, this is more old school, but I really believe in that and I think it makes such a big difference to people.

Q: One last question. When you think back over your career and the things you've accomplished, what do you think the biggest contributor to your success has been?

A:  Putting my head down and doing the work. And taking risks. Doing things which were not necessarily conventional. And just, you know, most important I think if you believe in something, and you know how to get there, it’s a lot of hard work but just putting your head down and doing it is the bottom line.

Q:  Great. All right, well before I let you go, I have my final five questions.

Q:  What's the best advice you've ever gotten?

A:  Don’t be afraid of taking a risk.

Q:  Okay. What does the word charged mean to you?

A:  Energized, motivated.

Q:  How do you recharge?

A:  Down time. You’ve got to disconnect, and disconnect completely. Yeah, do something completely different.

Q:  What's your favorite completely different?

A:  Walking my dog, spending time with my family, watch Food Network. Sounds corny, but I love that.

Q:  When and where are you happiest?

A:  I think at home with my family; my kids, my husband and my lab. I love it.

Q:  And what rituals help you have a successful day?

A:  My morning quiet coffee time just helps recalibrate my brain a little bit. Just thinking alone, yeah.

Q:  Thank you so much, Noopur. It's been truly a pleasure to talk with you today.

A:  Thanks, Amy.